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Adv Biomed Res 2012,  1:27

Viral and nonviral delivery systems for gene delivery

1 Molecular Genetic Laboratory, Alzahra Hospital; Pediatric Inherited Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Molecular Genetic Laboratory, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
3 Department of Clinical Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences and Health Services, Isfahan, Iran

Date of Submission13-Dec-2011
Date of Acceptance10-Mar-2012
Date of Web Publication06-Jul-2012

Correspondence Address:
Nouri Nayerossadat
Molecular Genetic Laboratory, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2277-9175.98152

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Gene therapy is the process of introducing foreign genomic materials into host cells to elicit a therapeutic benefit. Although initially the main focus of gene therapy was on special genetic disorders, now diverse diseases with different patterns of inheritance and acquired diseases are targets of gene therapy. There are 2 major categories of gene therapy, including germline gene therapy and somatic gene therapy. Although germline gene therapy may have great potential, because it is currently ethically forbidden, it cannot be used; however, to date human gene therapy has been limited to somatic cells. Although numerous viral and nonviral gene delivery systems have been developed in the last 3 decades, no delivery system has been designed that can be applied in gene therapy of all kinds of cell types in vitro and in vivo with no limitation and side effects. In this review we explain about the history of gene therapy, all types of gene delivery systems for germline (nuclei, egg cells, embryonic stem cells, pronuclear, microinjection, sperm cells) and somatic cells by viral [retroviral, adenoviral, adeno association, helper-dependent adenoviral systems, hybrid adenoviral systems, herpes simplex, pox virus, lentivirus, Epstein-Barr virus)] and nonviral systems (physical: Naked DNA, DNA bombardant, electroporation, hydrodynamic, ultrasound, magnetofection) and (chemical: Cationic lipids, different cationic polymers, lipid polymers). In addition to the above-mentioned, advantages, disadvantages, and practical use of each system are discussed.

Keywords: Chemical delivery, gene therapy, non viral delivery systems, physical delivery, viral delivery systems

How to cite this article:
Nayerossadat N, Maedeh T, Ali PA. Viral and nonviral delivery systems for gene delivery. Adv Biomed Res 2012;1:27

How to cite this URL:
Nayerossadat N, Maedeh T, Ali PA. Viral and nonviral delivery systems for gene delivery. Adv Biomed Res [serial online] 2012 [cited 2023 Apr 1];1:27. Available from:

  Introduction Top

Basically gene therapy is an intracellular delivery of genomic materials (transgene) into specific cells to generate a therapeutic effect by correcting an existing abnormality or providing the cells with a new function. [1] Different types of gene delivery systems may be applied in gene therapy to restore a specific gene function or turning off a special gene(s). The ultimate goal of gene therapy is single administration of an appropriate material to replace a defective or missing gene. [2] The first human gene transfer was utilized in 1989 on tumor-infiltrating lymphocytes [3],[4] and the first gene therapy was done on ADA gene for treatment of patients with SCID (Severe Combined Immunodeficiency Defect) in 1990. [5] Although initially the main focus of gene therapy was on inherited genetic disorders, now diverse diseases, including autosomal or X-linked recessive single gene disorders (CF(Cystic Fibrosis), ADA (Adenosine Deaminase) -SCID, emphysema, retinitis pigmentosa, sickle cell anemia, phenylketonuria, hemophilia, DMD (Duchenne Muscular Dystrophy), some autosomal dominant disorders, even polygenic disorders, different forms of cancers, vascular disease, neurodegenerative disorders, inflammatory conditions, and other acquired diseases are targets of gene therapy. To date, thousands of disorders have been treated by more than hundreds of protocols of gene therapy. [1] There are 2 major categories of gene therapy: Germline gene therapy and somatic gene therapy. Although germline gene therapy may have a great potential, because it is currently ethically forbidden, it cannot be used. [6],[7],[8] To date, human gene therapy has been limited to somatic cell alterations and there is a remarkable development in the field. There are different viral and nonviral vectors for gene delivery, but all gene therapy applications depend on the fact that the genetic material needs to be delivered across the cell membrane and ultimately to the cell nucleus. Each of the delivery systems has some advantages and disadvantages, and in this review we explain about all types of gene delivery systems briefly [Figure 1].
Figure 1: Different gene delivery systems

Click here to view

  Different Methods of Gene Therapy Top

Germline gene therapy

The technology of this type of gene therapy is simple as genetic abnormalities can be corrected by direct manipulation of germline cells with no targeting, and not only achieve a cure for the individual treated, but some gametes could also carry the corrected genotype. Although it almost never has been tested on humans, some different transgenic techniques have been used on other species, which include the following:

  1. Gene delivery to the nuclei taken from somatic cells at metaphase stage. [9],[10]
  2. Ex vivo alteration of egg cells, following in vitro fertilization. [11],[12]
  3. Manipulation of embryonic stem cells of mouse during in vitro culture by different gene delivery systems. [12],[13],[14]
  4. Pronuclear microinjection of exogenous DNA solution by a glass needle. [15]
  5. Transgenic delivery into sperm cells by direct or indirect injection to testis or other parts of the genital system. [16],[17]

Somatic gene therapy

Somatic gene therapy involves the insertion of genes into diploid cells of an individual where the genetic material is not passed on to its progeny. Somatic cell therapy is viewed as a more conservative, safer approach because it affects only the targeted cells in the patient, and is not passed on to future generations; however, somatic cell therapy is short-lived because the cells of most tissues ultimately die and are replaced by new cells. In addition, transporting the gene to the target cells or tissue is also problematic. Regardless of these difficulties, however, somatic cell gene therapy is appropriate and acceptable for many disorders.

There are 3 types of somatic gene therapy

Ex vivo delivery

In this system the genetic material is explanted from the target tissue or bone marrow, cultivated and manipulated in vitro, and then transducted and/or transfected into the target tissue. There are no immunologic problems in this way but only the technique is used in cases where the target cells act as protein secretion resources (like the treatment of ADA or hemophilia) or as a vaccine for cancer treatment, so there are major limitations on the use of ex vivo delivery. In addition, at present only a small percentage of reimplanted cells remain viable. [18],[19]

In situ delivery

The administration of the genetic material directly into the target tissue is in situ delivery. As most of the current delivery systems need no effective targeting, the way is proper. The system has been utilized in the delivery of CFTR gene by lipid and adenoviral vectors to a specific site in the respiratory tract and is also used in the treatment of different cancers. However, low efficiency of transduction is the main problem of this system, because in cancer therapy one malignant cell can re-establish the tumor again. [20],[21],[22]

In vivo delivery

The transfer of genetic material through an appropriate vector, which can be a viral or nonviral vector, into the target tissue is in vivo delivery. This technique is the least advanced strategy at present but potentially it might be the most useful. The problem of this way is insufficient targeting of vectors to the correct tissue sites; however, improvement in targeting and vector development will solve the problem.

  Different Vector Systems for Gene Delivery Top

Viral vectors

One of the successful gene therapy systems available today are viral vectors, such as retrovirus, adenovirus (types 2 and 5), adeno-associated virus, herpes virus, pox virus, human foamy virus (HFV), and lentivirus. [23] All viral vector genomes have been modified by deleting some areas of their genomes so that their replication becomes deranged and it makes them more safe, but the system has some problems, such as their marked immunogenicity that causes induction of inflammatory system leading to degeneration of transducted tissue; and toxin production, including mortality, the insertional mutagenesis; and their limitation in transgenic capacity size. [24],[25] During the past few years some viral vectors with specific receptors have been designed that could transfer the transgenes to some other specific cells, which are not their natural target cells (retargeting). [26]

Retroviral vectors

Retroviral vectors are one of the most frequently employed forms of gene delivery in somatic and germline gene therapies. Retroviruses in contrast to adenoviral and lentiviral vectors, can transfect dividing cells because they can pass through the nuclear pores of mitotic cells; this character of retroviruses make them proper candidates for in situ treatment. [27],[28] In addition, all of the viral genes have been removed, creating approximately 8 kb of space for transgenic incorporation. Retroviruses are useful for ex vivo delivery of somatic cells because of their ability to linearly integrate into host cell genome; for example, they have been used for human gene therapy of X-SCID successfully but incidence of leukemia in some patients occurred because of integration of retroviruses to the LMO2 gene and inappropriate activation of it. [29],[30],[31],[32],[33],[34] Retroviral vectors also have been applied for familial hyperlipidemia gene therapy and tumor vaccination. However, the main limitations of retroviral vectors are their low efficiency in vivo, immunogenic problems, the inability to transduce the nondividing cells and the risk of insertion, which could possibly cause oncogene activation or tumor-suppressor gene inactivation. [27],[28],[29],[30],[31],[32],[33],[34]

Adenoviral vectors

Adenoviral vectors have been isolated from a large number of different species, and more than 100 different serotypes have been reported. Most adults have been exposed to the adenovirus serotypes most commonly used in gene therapy (types 2 and 5). Adenoviruses type 2 and 5 can be utilized for transferring both dividing and nondividing cells and have low host specificity so can be used for gene delivery into large range of tissues. [35] Adenoviruses are able to deliver large DNA particles (up to 38 kb), [36] but in contrast to retroviruses, as they would not integrate into the host genome, their gene expression is too short term. Natural and acute immunologic responses against adenoviruses have made their clinical application limited to a few tissues, such as liver, lung (especially for CF(Cystic Fibrosis) treatment), or localized cancer gene therapy. Although the risk of serious disease following natural adenovirus infection is rare and the viral genome would not integrate into the host genome, gene therapy by adenoviral vectors has caused serious bad side effects and even death of some patients. [37],[38],[39],[40] Recently, in addition to safety of these vectors, several essential genes have been deleted so that viral replication can only occur under control and also most of the viral genome is deleted to obtain sufficient space for 38 kb of transgene particles, this kind of adenoviruses are called "gutless" or "pseudo" adenoviruses.

Adeno-associated vectors

Adeno-associated vectors (AAV) are like adenoviral vectors in their features but because of having some deficiency in their replication and pathogenicity, are safer than adenoviral vectors. [41] In human, AAVs are not associated with any disease. Another special character of AAV is their ability to integrate into a specific site on chromosome 19 with no noticeable effects cause long-term expression in vivo. The major disadvantages of these vectors are complicated process of vector production and the limited transgene capacity of the particles (up to 4.8 kb). AAVs have been used in the treatment of some diseases, such as CF, hemophilia B, Leber congenital amaurosis, and AAT (Alpha-1 antitrypsine) deficiency. [41],[42],[43],[44]

Helper-dependent adenoviral vector

Helper-dependent adenoviral vector (HdAd), called also as "gutless" or "gutted" vector, are last generation of adenovirus vectors. [35] The disadvantages of the first-generation AdV, such as a packaging capacity limitation (8 kb), immunogenicity, and toxicity, could be overcome, with the development of high-capacity "gutless" Advs (HC-AdV). In this helper-dependent vector system, one vector (the helper) contains all the viral genes required for replication but has a conditional gene defect in the packaging domain. The second vector contains only the ends of the viral genome, therapeutic gene sequences, and the normal packaging recognition signal, which allows selectively packaged release from cells. [46] Therefore, this helper-dependent system reduces toxicity but helps prolonged gene expression of up to 32 kb of foreign DNA in host cells. Nowadays, gutless adenovirus is administered in different organs, such as muscle, liver, and central nervous system. [45],[46],[47],[48],[49],[50],[51]

Hybrid adenoviral vectors

Hybrid adenoviral vectors are made of the high transduction efficiency of a gene-deleted adenoviral vector and the long-term genome-integrating potential of adeno-associated and retroviruses viruses. Such hybrid systems show stable transduction and limited integration sites. [52],[53] Among integrating vectors, those derived from retroviruses are most common. One of the family of Retroviridae are called spuma retroviruses or foamy viruses (FVs). FVs are a group of apparently nonpathogenic nonhuman retroviruses, which have been developed only recently. [54],[55] The potential advantages of FV vectors include a broad range of hosts, the largest packaging capacity of any retrovirus, and the ability to persist in quiescent cells. Because of these features, FVs have the unique potential to safely and efficiently deliver several genes into a number of different types of cells. [56],[57]

Herpes simplex virus

Herpes simplex virus (HSV) is one of the recent viruses candidate in gene delivery. HSV systems include the development of the so-called disabled infectious single copy (DISC) viruses, which comprise a glycoprotein H defective mutant HSV genome. When the defective HSV propagated in complementing cells' viral particles are generated, they can infect in subsequent cells permanently replicating their own genome but not producing more infectious particles. [58] Herpes vectors can deliver up to 150 kb transgenic DNA and because of its neuronotropic features, it has the greatest potential for gene delivery to nervous system, [59] tumors, and cancer cells. [60],[61],[62],[63],[64]


Lentiviruses are a subclass of retroviruses. They have recently been used as gene delivery vectors due to their ability to naturally integrate with nondividing cells, which is the unique feature of lentiviruses as compared with other retroviruses, which can infect only the dividing cells. Lentiviral vectors can deliver 8 kb of sequence. Because lentiviruses have strong tropism for neural stem cells, extensively used for ex vivo gene transfer in central nervous system with no significant immune responses and no unwanted side effects. Lentiviral vectors have the advantages of high-efficiency infection of dividing and nondividing cells, long-term stable expression of a transgene, low immunogenicity, and the ability to accommodate larger transgenes. [65],[66],[67]

There are numerous examples of effective long-term treatment of animal models of neurologic disorders, such as motor neuron diseases, Parkinson, Alzheimer, Huntington's disease, lysosomal storage diseases, and spinal injury. [68],[69],[70],[71],[72],[73]

Poxvirus vectors

Poxvirus vectors are members of the Poxviridae family that are widely used for high-level cytoplasmatic expression of transgenes. The high stable insertion capacity (more than 25 KB) of this virus is the most advantageous feature of it for gene delivery. The insertion of the transgene sequences is somewhat different from the other vector systems and utilizes homologous recombination or in vitro ligation for construction of recombinant vaccinia virus vectors. [74],[75],[76] Poxviruses have been used for cancer therapy in various studies, such as prostate cancer, colorectal cancer, breast cancer, and lung cancer. [77],[78] Recombinant vaccinia virus vectors were also used for expression of E6 and E7 0genes of human papilloma virus types 16 and 18 in cervical cancer patients to induce tumor regression. [79]

There are some problems in utilizing poxviruses for gene delivery because of their complex structure and biology, so further studies are required to improve their safety and to reduce the risk of cytopathic effects.

Epstein-Barr virus

Epstein-Barr virus as a herpes virus can be used for the expression of large DNA fragments in target cells. Because Epstein-Barr virus (EBV) establishes itself in the host nucleus in a latent state as extrachromosomal circular plasmid, this virus is suitable for long-term retention in the target cell. [80],[81],[82] Because of the natural B-cell tropism of the virus, EBV-derived vectors, such as B-cell lymphoma, have been tested for immune therapy of cancer. [83]

However, other types of viruses are under investigation to date and recently, many more different virus vector systems are being developed. These are derived from vaccinia virus, human cytomegalovirus, EBV, but as mentioned earlier, problems, such as their mutagen and carcinogen properties and long-term maintenance, are major limitations in utilizing the viral vectors in gene therapy.

  Nonviral Delivery Systems Top

Nonviral systems comprise all the physical and chemical systems except viral systems and generally include either chemical methods, such as cationic liposomes and polymers, or physical methods, such as gene gun, electroporation, particle bombardment, ultrasound utilization, and magnetofection. Efficiency of this system is less than viral systems in gene transduction, but their cost-effectiveness, availability, and more importantly less induction of immune system and no limitation in size of transgenic DNA compared with viral system have made them more effective for gene delivery than nonviral delivery systems to date. [84],[85]

Physical methods of nonviral gene delivery

Physical methods applied for in vitro and in vivo gene delivery are based on making transient penetration in cell membrane by mechanical, electrical, ultrasonic, hydrodynamic, or laser-based energy so that DNA entrance into the targeted cells is facilitated.

Naked DNA

Naked DNA alone is able to transfer a gene (2-19 kb) into skin, thymus, cardiac muscle, and especially skeletal muscle and liver cells when directly injected, [86],[87] also it has been applied directly. [87] Long-term expression has been observed in skeletal muscle following injection for more than 19 months. Single injection yields transgenic expression in less than 1% of total myofibers of the muscle but multiple injection would improve it. Although naked DNA injection is a safe and simple method, its efficiency for gene delivery is low so it is only proper for some applications, such as DNA vaccination.

DNA particle bombardant by gene gun

DNA particle bombardant by gene gun is an ideal alternative technique to injection of naked DNA. Gold or tungsten spherical particles (1-3 μm diameter) are coated with plasmid DNA and then accelerated to high speed by pressurized gas to penetrate into target tissue cells. [88] Actually it is a modification of a technique called "biolistic," originally developed for plant transgenesis, but now used for in vitro and in vivo gene delivery into mammalian cells too, [89],[90] such as skin, mucosa, or surgically exposed tissue and especially for DNA-based immunization or vaccination. [91]


Electroporation is temporary destabilization of the cell membrane targeted tissue by insertion of a pair of electrodes into it so that DNA molecules in the surrounding media of the destabilized membrane would be able to penetrate into cytoplasm and nucleoplasm of the cell [92],[93] but unfortunately the trangene can integrate only to 0.01% of the treated cells. [94] Electroporation has been used in vivo for many types of tissues, such as skin, muscle, lung, [95],[96],[97] HPRT gene delivery, [98] and tumor treatment. [99] There are some problems in this method too that the more important are the difficulty in surgical procedure in the placement of electrodes into the internal tissues and that the high voltage applied to tissue might damage the organ and affect genomic DNA stability. [100]


Hydrodynamic is a simple and highly efficient method for direct intracellular delivery of any water-soluble compounds and particles into internal organs. [101] The efficiency of this simple method in vivo is higher than any other nonviral system. This method has been successful for gene delivery into rodent liver and expression of hemophilia factors, [102] cytokines, [103] erythropoietin, [104] and hepatic growth factors, [105] in mouse and rat but it has been successful only in small animals and not in human.


Ultrasound can make some nanomeric pores in membrane to facilitate intracellular delivery of DNA particles into cells of internal organs or tumors, so the size and concentration of plasmid DNA have great role in efficiency of the system. [106],[107] The most important limitation of the system is low efficiency of it, especially in vivo.


Magnetofection is a simple and efficient transfection method that has the advantages of the nonviral biochemical (cationic lipids or polymers) and physical (electroporation, gene gun) transfection systems in one system while excluding their inconveniences, such as low efficiency and toxicity. In this method the magnetic fields are used to concentrate particles containing nucleic acid into the target cells. [108],[109] In this way, the magnetic force allows a very rapid concentration of the entire applied vector dose onto cells, so that 100% of the cells get in contact with a significant vector dose. Magnetofection has been adapted to all types of nucleic acids (DNA, siRNA, dsRNA, shRNA, mRNA, ODN,…), nonviral transfection systems (transfection reagents) and viruses. It has been successfully tested on a broad range of cell lines, hard-to-transfect and primary cells. [110],[111]

Chemical nonviral delivery systems

Chemical systems are more common than physical methods and generally are nanomeric complexes, which include compaction of negatively charged nucleic acid by polycationic nanomeric particles, belonging to cationic liposome/micelle or cationic polymers. The nanomeric complex between a cationic liposome or micelle and nucleic acids is called lipoplex; but polyplex is the nanomeric complex formed between a cationic polymer and nucleic acids. These nanomeric complexes are generally stable enough to produce their bound nucleic acids from degradation and are competent to enter cells usually by endocytosis. [112] Cationic nonviral delivery systems have several advantages compared to other nonviral systems and especially viral vectors, such as low toxicity and antigenicity because they are made of only biological lipids, long-term expression with less risk of insertional oncogenesis but still low efficiency is the disadvantage of this system as well. Generally cationic lipids are included in 6 subcategories:

(1) Monovalent cationic lipids

(2) Polyvalent cationic lipids

(3) Guanidine containing

(4) Cholesterol derivative compounds

(5) Cationic polymers: Poly(ethylenimine) (PEI)

Poly-l-lysine) (PLL)


Other cationic polymers [113]

(6) Lipid-polymer hybrid

Mechanism of gene delivery by cationic particles

The mechanism of gene delivery by cationic systems includes 4 steps:

  1. Nonspecific interaction between cationic particles and cell surface
  2. Endocytosis into endocytosis vesicles (endosomes)
  3. Compaction and release of the DNA particle from endosomes
  4. Translocation of the DNA particle to nucleus by membrane receptors and transgenic expression of it. [114]

For targeting of cationic particles various cell-targeting legends are covalently attached to a lipid anchor (in lipoplexes) or a DNA-binding cationic polymer (in polyplexes), [115] including proteins, [116],[117],[118] antibodies, [119],[120] small chemical compounds, [121] carbohydrates, [122] peptide ligands, [123] and vitamins, [124] some of these ligands have enhanced the vector efficiency from 10- to 1000-folds. When lipoplex or polyplex particles made association with cell surface, they would enter the cell by endocytosis. It seems more of the lipid particles in early endosomes become trapped in lysosomes and degenerate by nucleases so the interaction of endosome with lysosome is a consensus and lipoplex or polyplex particles should be released before contraction of lysosome to endosome, so fugenic peptides can help it, these peptides originating from viruses can cut off the endosomal membrane to release the genomic DNA leading to increase of genetic translocation efficiency of the liposome. [125]

In this section we focus mainly on the 2 most common cationic particles: Cationic lipids and cationic polymers:

Cationic liposomes

Cationic liposomes are the more important current nonviral polycationic systems, which compact negatively charged nucleic acids lead to the formation of nanomeric complexes. Cationic liposomes have unique characteristics, such as capability to incorporate hydrophilic and hydrophobic drugs, low toxicity, no activation of immune system, and targeted delivery of bioactive compounds to the site of action. [126],[127],[128],[129] But the rapid degradation of liposomes due to the reticuloendothelial system and the inability to achieve sustained drug delivery over a prolonged period of time are 2 drawbacks of these delivery systems that have been overcome by modification of the surface of liposomes with hydrophilic polymers, such as polyethylene glycol (PEG) [128] and integration of the pre-encapsulated drug-loaded liposomes within depot polymer-based systems. [130]

All liposomes have 1 or 2 fatty acids and alkyl moieties that are 12-18 carbons in length, in addition to a positively charged polar head group hydrophobic groups, this hydrophobic structure causes the cationic lipids. Since the first monovalent cationic lipid, DOTAP, was synthesized by Felgner et al. in 1987, [131] hundreds of new cationic liposome/micelle systems have been reported for gene delivery in vitro or in vivo. The routine way to prepare a lipoplex is mixing the solution of plasmid DNA and liposome in a proper buffer. The gene delivery efficiency of liposomes is dependent on the size, structure, and even the amount of the liposome, the charge ratio between transgenic DNA and cationic liposome, presence of helper lipid, and the structure and proportion of it and cell type.

As mentioned earlier, cationic systems are mad of either a single synthetic cationic amphiphile (cytofectin), such as DOTAP, DOTMA, DOSPA, DOGS, or more commonly of a combination of a cationic amphiphile and a neutral lipid, such as DOPE and cholesterol, these neutral helper lipids unstabilize the endosomal membrane to facilitate lipid exchange and membrane fusion between lipoplexes and endosomal membrane leading to more gene expression. [132],[133] Cationic liposome-mediated delivery of DNA materials is optimal in vivo when the mol ratio of cationic liposome to nucleic acid in the lipoplex mixture is such that the positive/negative charge ratio is around 1 or greater [134],[135],[136] and in vitro the optimal ratio is closer to 1. [137],[138],[139],[140] However, multivalent lipids with long and unsaturated hydrocarbon chains are more efficient than monovalent cationic lipids with the same hydrophobic chains. [141]

Cationic liposomes are being used in gene delivery into lung, skeletal muscles, spleen, kidney, liver, testis, heart, and skin cells. [141],[142],[143],[144],[145],[146],[147],[148]

For gene transfer in vivo, many complexes (in equimolar ratios) are used that the more general ones are Chol/DOPE (1:1), DOTMA/DOPE (1:1), and DOTAP/DOPE (1:1).

Liposome-based technology has progressed from the first-generation conventional vesicles to stealth liposomes, targeted liposomes, and more recently stimuli-sensitive liposomes. [149],[150] These new generation of liposomes overcome most of the challenges encountered by conventional liposomes, such as the inability to escape from immune system, toxicity due to charged liposomes, and low half-life stability. [151],[152],[153]

Cationic polymers

Cationic polymers at first were introduced by Wu et al.1987 184 as PLL, the same year of synthesizing the first cationic lipids, and were further expanded by a second generation, PEI by Behr et al. in 1995. [154] To date a variety of linear or branched cationic polymers have been synthesized, including PLL-containing peptides, endosomolytic peptides (histidine-rich peptides), fusogenic peptides, nuclear localization peptides (mono partite NLS(Nuclear localization signal), bipartite NLS, nonclassical NLS), proteosomes. [155] However, PLL is still the most widely studied cationic polymer and has been used in a variety of polymerizations of lysine ranging from 19 to 1116 amino acid residues (3.97-233.2 kDa). While the molecular weight of the polymer increases, the net positive charge of it also increases and are therefore able to bind DNA tighter and form more stable complexes, totally. There is a relationship between the length of the polymer, gene delivery efficiency, and toxicity as the length of the polymer increases, so does its efficiency and its toxicity. [155],[156] However, the efficiency of PLL-mediated polyplexes are low when the PLL is used alone so some conjugation agents are used to facilitate cellular uptake in vitro (as EGF(fibroblast growth factor) or transferring) or endosomal escape in vivo (as fusogenic peptides or defective viruses). Also the attachment of PEG to the polymer can prevent plasma protein binding and increase circulation of half-life of the complex. [157],[158] Different homogenous PLL-conjugated peptides have been developed that have low toxicity, higher efficiency, and site-specific attachment of ligands used for cell targeting. [159],[160],[161],[162] The optimal peptide sequence contains 18 lysines followed by a tryptophan and alkylated cysteine (AlkCWK18). A variety of branched forms of cationic peptides with a lysine as branching point have been explored. [162] PEI is the most important cationic polymer next to PLL. PEI is one of the most positively charged dense polymers, synthesized in linear (LPEI) or branched (BPEI) form, which have high transfection activity in vitro and moderate activity in vivo but the linear forms have low toxicity and high efficiency than branched forms. [163] As PLL, conjugation of some agents, such as galactose, anti-CD3 antibodies and RGD motif-containing peptides can facilitate PEI polyplex cellular uptake. [164],[165],[166] Two advantages of PEI is that it forms toroidal polyplex particles, which are stable to aggregation in physiological buffer conditions, PEI also has a strong buffering capacity at almost any pH because of the great number of primary, secondary, and tertiary amino groups. [167] One disadvantage of PEI is its nonbiodegradable nature [168] and its serious toxicity in vivo (in contrast to cationic liposome/micelle). There are conflicting associations between the gene delivery efficiency and PEI toxicity, such as PLL, the most active PEI is 25 k for BPEI and 22 k for LPEI. [169] Unfortunately, due to this property there are some limitations in the application of PEI in nonviral vector in vivo delivery. More biodegradable cationic polymers, such as aminoesters have been explored that have less toxicity than PEI and PLL. [170] However, as mentioned earlier, there are a variety of new cationic polymer groups but each of them have some advantages and disadvantages. [155] The notable factors for in vivo application are toxicity and transfection efficiency.

Lipid-polymer systems

Lipid-polymer systems are 3-part systems in which DNA is first precondensed with polycations and then coated with either cationic liposomes, anionic liposomes, or amphiphilic polymers with or without helper lipids. [171],[172],[173],[174]

  Conclusion Top

Although numerous viral and nonviral gene delivery systems have been developed in the last 3 decades, all of them have some disadvantages that have made some limitations in their clinical application and yet no delivery system has been designed that can be applied in gene therapy of all kinds of cell types in vitro and in vivo with no limitation and side effects; however, some delivery systems has been explored, which can be efficient for gene delivery to specific cells or tissues. So it seems that the process of developing successful delivery systems, especially nonviral systems, for use in in vivo is still in its adolescence and more efforts are needed. Totally, key steps effective in improving the currently available systems include the following: (1) improving extracellular targeting and delivery, (2) enhancing intracellular delivery and long-time expression, and (3) reducing toxicity and side effects on human body. However, clinical successes in 2009-2011 have bolstered new optimism in the promise of gene therapy. These include successful treatment of patients with the retinal disease Leber congenital amaurosis, [175],[176],[177],[178] X-linked SCID, [179] ADA-SCID, [180] adrenoleukodystrophy, [180] and Parkinson's disease. [181]

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202 Efficient drug and gene delivery to liver fibrosis: rationale, recent advances, and perspectives
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203 In situ Bone Tissue Engineering using Gene Delivery Nanocomplexes
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218 Optimization of electroporation and other non-viral gene delivery strategies for T cells
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219 Engineering Biomimetic Materials for Skeletal Muscle Repair and Regeneration
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220 Effects of human placenta-derived mesenchymal stem cells with NK4 gene expression on glioblastoma multiforme cell lines
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226 Osteogenic Effects of VEGF-Overexpressed Human Adipose-Derived Stem Cells with Whitlockite Reinforced Cryogel for Bone Regeneration
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229 DNA vaccination via RALA nanoparticles in a microneedle delivery system induces a potent immune response against the endogenous prostate cancer stem cell antigen
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230 LINGO-1 siRNA nanoparticles promote central remyelination in ethidium bromide-induced demyelination in rats
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231 Creatine based polymer for codelivery of bioengineered MicroRNA and chemodrugs against breast cancer lung metastasis
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235 Recent Progress of Polymeric Nanogels as Nucleic Acid Delivery Systems
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236 Liposomal delivery of functional transmembrane ion channels into the cell membranes of target cells; A potential approach for the treatment of channelopathies
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237 An insight into non-integrative gene delivery approaches to generate transgene-free induced pluripotent stem cells
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239 Lipid gene nanocarriers for the treatment of skin diseases: Current state-of-the-art
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240 Modified gelatin nanoparticles for gene delivery
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241 RNA-Guided Adenosine Deaminases: Advances and Challenges for Therapeutic RNA Editing
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244 Recombinant AAV-CEA Tumor Vaccine in Combination with an Immune Adjuvant Breaks Tolerance and Provides Protective Immunity
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247 Contributions of VPS35 Mutations to Parkinson’s Disease
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248 Exosomes Derived from miR-126-modified MSCs Promote Angiogenesis and Neurogenesis and Attenuate Apoptosis after Spinal Cord Injury in Rats
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259 Antibody-targeted chromatin enables effective intracellular delivery and functionality of CRISPR/Cas9 expression plasmids
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Nucleic Acids Research. 2019;
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260 Gene Therapy for Inherited Retinal Degeneration
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Journal of Ocular Pharmacology and Therapeutics. 2019;
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261 Gene delivery into hepatic cells with ternary complexes of plasmid DNA, cationic liposomes and apolipoprotein E-derived peptide
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Experimental and Therapeutic Medicine. 2019;
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262 Biomaterial substrate modifications that influence cell-material interactions to prime cellular responses to nonviral gene delivery
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263 Protein-based vehicles for biomimetic RNAi delivery
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Journal of Biological Engineering. 2019; 13(1)
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264 Nucleic acid delivery to mesenchymal stem cells: a review of nonviral methods and applications
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265 Neuroglobin Expression Models as a Tool to Study Its Function
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Oxidative Medicine and Cellular Longevity. 2019; 2019: 1
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266 CRISPR/Cas System for Genome Editing: Progress and Prospects as a Therapeutic Tool
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268 Recent advances in the development of gene delivery systems
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269 The Delivery of Personalised, Precision Medicines via Synthetic Proteins
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270 Advances in Targeted Gene Delivery
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271 Designer Nucleases: Gene-Editing Therapies using CCR5 as an Emerging Target in HIV
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Current HIV Research. 2019; 17(5): 306
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272 Long Noncoding RNAs in Acute Myeloid Leukemia: Functional Characterization and Clinical Relevance
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Cancers. 2019; 11(11): 1638
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273 Cancer Treatment Goes Viral: Using Viral Proteins to Induce Tumour-Specific Cell Death
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274 Telomere Gene Therapy: Polarizing Therapeutic Goals for Treatment of Various Diseases
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Cells. 2019; 8(5): 392
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275 miRNAs in gastrointestinal diseases: can we effectively deliver RNA-based therapeutics orally?
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276 Lipidoid iron oxide nanoparticles are a platform for nucleic acid delivery to the liver
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277 ?????????????? ??????????? ?????? ?????? ??? ????????? ??? ???????? ??????????? ?????? ? ??????
?. ?. ???????,?. ?. ???????,?. ?. ????????,?. ?. ??????????,?. ?. ?????????,?. ?. ?????????,?. ?. ???????????,?. ?. ???????,?. ?. ??????
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278 Novel Delivery Systems for Checkpoint Inhibitors
Purushottam Lamichhane,Rahul Deshmukh,Julie A. Brown,Silvia Jakubski,Priyanka Parajuli,Todd Nolan,Dewan Raja,Mary Badawy,Thomas Yoon,Mark Zmiyiwsky,Narottam Lamichhane
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279 Electrospinning Nanofibers for Therapeutics Delivery
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280 Plant/Bacterial Virus-Based Drug Discovery, Drug Delivery, and Therapeutics
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281 Chitosan in Non-Viral Gene Delivery: Role of Structure, Characterization Methods, and Insights in Cancer and Rare Diseases Therapies
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282 Intravenous Delivery of piggyBac Transposons as a Useful Tool for Liver-Specific Gene-Switching
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283 Rational Design of a siRNA Delivery System: ALOX5 and Cancer Stem Cells as Therapeutic Targets
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284 Recombinant Histones as an Instrument for the Delivery of Nucleic Acids into Eukaryotic Cells
M. V. Zinovyeva,A. V. Sass,A. V. Vvedensky,V. K. Potapov,L. G. Nikolaev,E. D. Sverdlov
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285 Cell-Penetrating Peptides to Enhance Delivery of Oligonucleotide-Based Therapeutics
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286 Combined use of plasmid drug pCMV-VEGFA and autodermoplasty for stimulation of skin defects healing in the experiment
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287 Directed myogenic reprogramming of differentiated cells
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288 Desarrollo de vectores génicos basados en polímeros sintéticos: PEI y PDMAEMA
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289 Recombinant histones as an instrument for delivery of nucleic acids into eukaryotic cells
M. V. Zinovyeva,A. V. Sass,A. V. Vvedensky,V. K. Potapov,L. G. Nikolaev,E. D. Sverdlov
Molecular Genetics Microbiology and Virology (Russian version). 2018; 36(3): 30
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290 Recent advances in stem cell therapeutics and tissue engineering strategies
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291 Membrane permeabilizing amphiphilic peptide delivers recombinant transcription factor and CRISPR-Cas9/Cpf1 ribonucleoproteins in hard-to-modify cells
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292 Myoediting: Toward Prevention of Muscular Dystrophy by Therapeutic Genome Editing
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293 Efficient Nonviral Transfection of Human Bone Marrow Mesenchymal Stromal Cells Shown Using Placental Growth Factor Overexpression
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294 Cell surface engineering and application in cell delivery to heart diseases
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295 Therapeutic effects of a mesenchymal stem cell-based insulin-like growth factor-1/enhanced green fluorescent protein dual gene sorting system in a myocardial infarction rat model
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296 Evaluating Nonintegrating Lentiviruses as Safe Vectors for Noninvasive Reporter-Based Molecular Imaging of Multipotent Mesenchymal Stem Cells
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297 Poly-l-lysine-coated superparamagnetic nanoparticles: a novel method for the transfection of pro-BDNF into neural stem cells
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Artificial Cells, Nanomedicine, and Biotechnology. 2018; : 1
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298 Enhanced gene transfection efficiency by low-dose 25?kDa polyethylenimine by the assistance of 1.8?kDa polyethylenimine
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299 Polyethylenimine-based nanocarriers in co-delivery of drug and gene: a developing horizon
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300 Live attenuated influenza vaccine viral vector induces functional cytotoxic T-cell immune response against foreign CD8+ T-cell epitopes inserted into NA and NS1 genes using the 2A self-cleavage site
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Human Vaccines & Immunotherapeutics. 2018;
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301 Enhanced transfection of a macromolecular lignin-based DNA complex with low cellular toxicity
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302 Successful reprogramming of cellular protein production through mRNA delivered by functionalized lipid nanoparticles
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303 The method of chicken whole embryo culture using the eggshell windowing, surrogate eggshell and ex ovo culture system
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British Poultry Science. 2018; : 1
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304 Current viral-mediated gene transfer research for treatment of Alzheimer’s disease
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305 Hepatocellular targeted a-tocopherol based pH sensitive galactosylated lipids: design, synthesis and transfection studies
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306 Transfection efficiencies of a-tocopherylated cationic gemini lipids with hydroxyethyl bearing headgroups under high serum conditions
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Organic & Biomolecular Chemistry. 2018;
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307 A siRNA-induced peptide co-assembly system as a peptide-based siRNA nanocarrier for cancer therapy
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308 PEGylated Chitosan for Nonviral Aerosol and Mucosal Delivery of the CRISPR/Cas9 System in Vitro
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309 A Universal GSH-Responsive Nanoplatform for the Delivery of DNA, mRNA, and Cas9/sgRNA Ribonucleoprotein
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310 Engineering Human Epidermal Growth Receptor 2-Targeting Hepatitis B Virus Core Nanoparticles for siRNA Delivery in Vitro and in Vivo
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311 BMP2 expressing genetically engineered mesenchymal stem cells on composite fibrous scaffolds for enhanced bone regeneration in segmental defects
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Materials Science and Engineering: C. 2018;
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312 RNA Structure Design Improves Activity and Specificity of trans -Splicing-Triggered Cell Death in a Suicide Gene Therapy Approach
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313 The determination of gemini surfactants used as gene delivery agents in cellular matrix using validated tandem mass spectrometric method
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314 Inhalable particulate drug delivery systems for lung cancer therapy: Nanoparticles, microparticles, nanocomposites and nanoaggregates
Hadeer M. Abdelaziz,Mohamed Gaber,Mahmoud M. Abd-Elwakil,Moustafa T. Mabrouk,Mayada M. Elgohary,Nayra M. Kamel,Dalia M. Kabary,May S. Freag,Magda W. Samaha,Sana M. Mortada,Kadria A. Elkhodairy,Jia-You Fang,Ahmed O. Elzoghby
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315 Exosomes: natural nanoparticles as bio shuttles for RNAi delivery
Saber Ghazizadeh Darband,Mohammad Mirza-Aghazadeh-Attari,Mojtaba Kaviani,Ainaz Mihanfar,Shirin Sadighparvar,Bahman Yousefi,Maryam Majidinia
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316 In vivo methods for acute modulation of gene expression in the central nervous system
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317 Gene-silencing suppressors for high-level production of the HIV-1 entry inhibitor griffithsin in Nicotiana benthamiana
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Process Biochemistry. 2018;
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318 Beyond gene transfection with methacrylate-based polyplexes – the influence of the amino substitution pattern
Ulrich S. Schubert,Tanja Bus,Martin Reifarth,Johannes C. Brendel,Stephanie Hoeppener,Anja Traeger,Anne-Kristin Trützschler
Bioconjugate Chemistry. 2018;
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319 Electrostatically assembled dendrimer complex with a high-affinity protein binder for targeted gene delivery
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320 Design of PEI-conjugated bio-reducible polymer for efficient gene delivery
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321 Structure-activity relationship of serotonin derived tocopherol lipids
Venkanna Muripiti,Thasneem Yoosuf Mujahid,Venkata Harsha Vardhan Boddeda,Shrish Tiwari,Srujan Kumar Marepally,Srilakshmi V Patri,Vijaya Gopal
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322 Nucleic-acid based gene therapy approaches for sepsis
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European Journal of Pharmacology. 2018;
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323 Bombesin/oligoarginine fusion peptides for gastrin releasing peptide receptor (GRPR) targeted gene delivery
Anjuman Ara Begum,Yu Wan,Istvan Toth,Peter M. Moyle
Bioorganic & Medicinal Chemistry. 2018; 26(2): 516
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324 Preparation of gene drug delivery systems of Cationic peptide lipid with 0G-PAMAM as hydrophilic end and its biological properties evaluation
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325 Acylation of the S413-PV cell-penetrating peptide as a means of enhancing its capacity to mediate nucleic acid delivery: Relevance of peptide/lipid interactions
Catarina M. Morais,Ana M. Cardoso,Pedro P. Cunha,Luísa Aguiar,Nuno Vale,Emílio Lage,Marina Pinheiro,Cláudia Nunes,Paula Gomes,Salette Reis,M. Margarida C.A. Castro,Maria C. Pedroso de Lima,Amália S. Jurado
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326 Gene therapy and type 1 diabetes mellitus
Dinesh Kumar Chellappan,Nandhini S. Sivam,Kai Xiang Teoh,Wai Pan Leong,Tai Zhen Fui,Kien Chooi,Nico Khoo,Fam Jia Yi,Jestin Chellian,Lim Lay Cheng,Rajiv Dahiya,Gaurav Gupta,Gautam Singhvi,Srinivas Nammi,Philip Michael Hansbro,Kamal Dua
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327 Crustacean nuclear localization signals help facilitating the delivery of DNA into Australian red-claw crayfish cells
Chan D.H. Nguyen,Tomer Ventura,Abigail Elizur
Aquaculture. 2018;
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328 Engineering DNA vaccines against infectious diseases
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329 Therapeutic potential of combined viral transduction and CRISPR/Cas9 gene editing in treating neurodegenerative diseases
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330 Comparison of random and gradient amino functionalized poly(2-oxazoline)s: Can the transfection efficiency be tuned by the macromolecular structure?
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Journal of Polymer Science Part A: Polymer Chemistry. 2018;
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331 Poloxamers, poloxamines and polymeric micelles: Definition, structure and therapeutic applications in cancer
Mauro Almeida,Mariana Magalhães,Francisco Veiga,Ana Figueiras
Journal of Polymer Research. 2018; 25(1)
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332 Engineering and cytosolic delivery of a native regulatory protein and its variants for modulation of ERK2 signaling pathway
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Biotechnology and Bioengineering. 2018;
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333 Mechanisms of unprimed and dexamethasone-primed nonviral gene delivery to human mesenchymal stem cells
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334 Multimeric Amphipathic a-Helical Sequences for Rapid and Efficient Intracellular Protein Transport at Nanomolar Concentrations
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335 Roles of microRNAs in T cell immunity: Implications for strategy development against infectious diseases
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336 Engineering brown fat into skeletal muscle using ultrasound-targeted microbubble destruction gene delivery in obese Zucker rats: Proof of concept design
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337 Mesenchymal stem cells: A new platform for targeting suicide genes in cancer
Rana Moradian Tehrani,Javad Verdi,Mahdi Noureddini,Rasoul Salehi,Reza Salarinia,Meysam Mosalaei,Miganosh Simonian,Behrang Alani,Moosa Rahimi Ghiasi,Mahmoud Reza Jaafari,Hamed Reza Mirzaei,Hamed Mirzaei
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338 Glycosaminoglycan and Proteoglycan-Based Biomaterials: Current Trends and Future Perspectives
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339 Plant viral and bacteriophage delivery of nucleic acid therapeutics
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340 Retro-inverso d -peptide-modified hyaluronic acid/bioreducible hyperbranched poly(amido amine)/pDNA core-shell ternary nanoparticles for the dual-targeted delivery of short hairpin RNA-encoding plasmids
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341 Fluorescent nanoswitch for monitoring specific pluripotency-related microRNAs of induced pluripotent stem cells: Development of polyethyleneimineoligonucleotide hybridization probes
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342 Exosome-based small RNA delivery: progress and prospects
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343 Modulating angiogenesis with integrin-targeted nanomedicines
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344 Insights into the key roles of epigenetics in matrix macromolecules-associated wound healing
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345 Functional therapies for cutaneous wound repair in epidermolysis bullosa
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346 Targeting renal fibrosis: Mechanisms and drug delivery systems
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347 Sustained viral gene delivery from a micro-fibrous, elastomeric cardiac patch to the ischemic rat heart
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348 Boron nitride nanotubes for gene silencing
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350 Integrated microfluidic devices for the synthesis of nanoscale liposomes and lipoplexes
Tiago A. Balbino,Juliana M. Serafin,Allan Radaic,Marcelo B. de Jesus,Lucimara G. de la Torre
Colloids and Surfaces B: Biointerfaces. 2017;
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351 Composite liposome-PEI/nucleic acid lipopolyplexes for safe and efficient gene delivery and gene knockdown
Shashank Reddy Pinnapireddy,Lili Duse,Boris Strehlow,Jens Schäfer,Udo Bakowsky
Colloids and Surfaces B: Biointerfaces. 2017;
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352 Recent advances on extracellular vesicles in therapeutic delivery: challenges, solutions, and opportunities
Mei Lu,Haonan Xing,Zhen Yang,Yanping Sun,Tianzhi Yang,Xiaoyun Zhao,Cuifang Cai,Dongkai Wang,Pingtian Ding
European Journal of Pharmaceutics and Biopharmaceutics. 2017;
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353 Adenovirus-mediated gene delivery: Potential applications for gene and cell-based therapies in the new era of personalized medicine
Cody S. Lee,Elliot S. Bishop,Ruyi Zhang,Xinyi Yu,Evan M. Farina,Shujuan Yan,Chen Zhao,Zongyue Zeng,Yi Shu,Xingye Wu,Jiayan Lei,Yasha Li,Wenwen Zhang,Chao Yang,Ke Wu,Ying Wu,Sherwin Ho,Aravind Athiviraham,Michael J. Lee,Jennifer Moriatis Wolf,Russell R. Reid,Tong-Chuan He
Genes & Diseases. 2017; 4(2): 43
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354 Improved formulation of cationic solid lipid nanoparticles displays cellular uptake and biological activity of nucleic acids
Anna Fàbregas,Silvia Prieto-Sánchez,Marc Suñé-Pou,Sofía Boyero-Corral,Josep Ramón Ticó,Encarna García-Montoya,Pilar Pérez-Lozano,Montserrat Miñarro,Josep Mª Suñé-Negre,Cristina Hernández-Munain,Carlos Suñé
International Journal of Pharmaceutics. 2017; 516(1-2): 39
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355 Surfactant effect on the physicochemical characteristics of cationic solid lipid nanoparticles
Chiara Botto,Nicolò Mauro,Erika Amore,Elisabetta Martorana,Gaetano Giammona,Maria Luisa Bondì
International Journal of Pharmaceutics. 2017; 516(1-2): 334
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356 Modifying plasmid-loaded HSA-nanoparticles with cell penetrating peptides – Cellular uptake and enhanced gene delivery
J. Mesken,A. Iltzsche,D. Mulac,K. Langer
International Journal of Pharmaceutics. 2017; 522(1-2): 198
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357 Synthesis and Degradation Study of Cationic Polycaprolactone-Based Nanoparticles for Biomedical and Industrial Applications
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Industrial & Engineering Chemistry Research. 2017; 56(20): 5872
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358 Polyplex Evolution: Understanding Biology, Optimizing Performance
Arnaldur Hall,Ulrich Lächelt,Jiri Bartek,Ernst Wagner,Seyed Moein Moghimi
Molecular Therapy. 2017;
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359 Pharmacological Reprogramming of Somatic Cells for Regenerative Medicine
Min Xie,Shibing Tang,Ke Li,Sheng Ding
Accounts of Chemical Research. 2017;
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360 Generation and Characterization of Virus-Enhancing Peptide Nanofibrils Functionalized with Fluorescent Labels
Sascha Rode,Manuel Hayn,Annika Röcker,Stefanie Sieste,Markus Lamla,Daniel Markx,Christoph Meier,Frank Kirchhoff,Paul Walther,Marcus Fändrich,Tanja Weil,Jan Münch
Bioconjugate Chemistry. 2017; 28(4): 1260
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361 Evolution of New “Bolaliposomes” using Novel a-Tocopheryl Succinate Based Cationic Lipid and 1,12-Disubstituted Dodecane-Based Bolaamphiphile for Efficient Gene Delivery
Mallikarjun Gosangi,Hithavani Rapaka,Venkatesh Ravula,Srilakshmi V. Patri
Bioconjugate Chemistry. 2017;
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362 The evolution of heart failure with reduced ejection fraction pharmacotherapy: What do we have and where are we going?
Ahmed Selim,Ronald Zolty,Yiannis S. Chatzizisis
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363 Interactions between microRNAs and long non-coding RNAs in cardiac development and repair
Alessio Rotini,Ester Martínez-Sarrà,Enrico Pozzo,Maurilio Sampaolesi
Pharmacological Research. 2017;
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364 Hydrodynamic gene delivery in human skin using a hollow microneedle device
M Dul,M Stefanidou,P Porta,J Serve,C OæMahony,B Malissen,S Henri,Y Levin,E Kochba,FS Wong,C Dayan,SA Coulman,JC Birchall
Journal of Controlled Release. 2017;
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365 Polymeric nanoparticles as cancer-specific DNA delivery vectors to human hepatocellular carcinoma
Camila G. Zamboni,Kristen L. Kozielski,Hannah J. Vaughan,Maisa M. Nakata,Jayoung Kim,Luke J. Higgins,Martin G. Pomper,Jordan J. Green
Journal of Controlled Release. 2017;
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366 Advances in the design of solid lipid nanoparticles and nanostructured lipid carriers for targeting brain diseases
Christos Tapeinos,Matteo Battaglini,Gianni Ciofani
Journal of Controlled Release. 2017;
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367 Genetically modified mesenchymal stem/stromal cells transfected with adiponectin gene can stably secrete adiponectin
Md. Murad Hossain,Malliga Raman Murali,Tunku Kamarul
Life Sciences. 2017; 182: 50
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368 Acceleration of bone regeneration in bioactive glass/gelatin composite scaffolds seeded with bone marrow-derived mesenchymal stem cells over-expressing bone morphogenetic protein-7
Saeid Kargozar,Seyed Jafar Hashemian,Mansooreh Soleimani,Peiman Brouki Milan,Mohammad Askari,Vahid Khalaj,Ali Samadikuchaksaraie,Sepideh Hamzehlou,Amir Reza Katebi,Noorahmad Latifi,Masoud Mozafari,Francesco Baino
Materials Science and Engineering: C. 2017; 75: 688
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369 Freezing-Assisted Gene Delivery Combined with Polyampholyte Nanocarriers
Sana Ahmed,Tadashi Nakaji-Hirabayashi,Takayoshi Watanabe,Takahiro Hohsaka,Kazuaki Matsumura
ACS Biomaterials Science & Engineering. 2017;
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370 Green Transfection: Cationic Lipid Nanocarrier System Derivatized from Vegetable Fat, Palmstearin Enhances Nucleic Acid Transfections
Priya Dharmalingam,Hari Krishna R. Rachamalla,Brijesh Lohchania,Bhanuprasad Bandlamudi,Saravanabhavan Thangavel,Mohankumar K. Murugesan,Rajkumar Banerjee,Arabinda Chaudhuri,Chandrashekhar Voshavar,Srujan Marepally
ACS Omega. 2017; 2(11): 7892
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371 Method for Dual Viral Vector Mediated CRISPR-Cas9 Gene Disruption in Primary Human Endothelial Cells
Haixia Gong,Menglin Liu,Jeff Klomp,Bradley J. Merrill,Jalees Rehman,Asrar B. Malik
Scientific Reports. 2017; 7: 42127
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372 Basic concepts and recent advances in nanogels as carriers for medical applications
Iordana Neamtu,Alina Gabriela Rusu,Alina Diaconu,Loredana Elena Nita,Aurica P. Chiriac
Drug Delivery. 2017; 24(1): 539
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373 Ternary complex of plasmid DNA with NLS-Mu-Mu protein and cationic niosome for biocompatible and efficient gene delivery: a comparative study with protamine and lipofectamine
Mohammad Hadi Nematollahi,Masoud Torkzadeh-Mahanai,Abbas Pardakhty,Hossein Ali Ebrahimi Meimand,Gholamreza Asadikaram
Artificial Cells, Nanomedicine, and Biotechnology. 2017; : 1
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374 Gene therapies development: slow progress and promising prospect
Eve Hanna,Cécile Rémuzat,Pascal Auquier,Mondher Toumi
Journal of Market Access & Health Policy. 2017; 5(1): 1265293
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375 Synthesis of magnetic cytosine-imprinted chitosan nanoparticles
Mei-Hwa Lee,Arti Ahluwalia,Jian-Zhou Chen,Neng-Lang Shih,Hung-Yin Lin
Nanotechnology. 2017; 28(8): 085705
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376 Combining Gene and Stem Cell Therapy for Peripheral Nerve Tissue Engineering
Francesca Busuttil,Ahad A. Rahim,James B. Phillips
Stem Cells and Development. 2017;
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377 Concise Review: The Potential Use of Intestinal Stem Cells to Treat Patients with Intestinal Failure
Sung Noh Hong,James C.Y. Dunn,Matthias Stelzner,Martín G. Martín
STEM CELLS Translational Medicine. 2017; 6(2): 666
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378 Bioengineered liposome–scaffold composites as therapeutic delivery systems
Claudia Zylberberg,Sandro Matosevic
Therapeutic Delivery. 2017; 8(6): 425
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379 Stimuli-Regulated Smart Polymeric Systems for Gene Therapy
Ansuja Mathew,Ki-Hyun Cho,Saji Uthaman,Chong-Su Cho,In-Kyu Park
Polymers. 2017; 9(4): 152
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380 Polyamidoamine (PAMAM) Dendrimers Modified with Cathepsin-B Cleavable Oligopeptides for Enhanced Gene Delivery
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Polymers. 2017; 9(6): 224
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381 A mechanistic investigation exploring the differential transfection efficiencies between the easy-to-transfect SK-BR3 and difficult-to-transfect CT26 cell lines
Elizabeth Figueroa,Pallavi Bugga,Vishwaratn Asthana,Allen L. Chen,J. Stephen Yan,Emily Reiser Evans,Rebekah A. Drezek
Journal of Nanobiotechnology. 2017; 15(1)
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382 Block copolymer conjugated Au-coated Fe3O4 nanoparticles as vectors for enhancing colloidal stability and cellular uptake
Junbo Li,Sheng Zou,Jiayu Gao,Ju Liang,Huiyun Zhou,Lijuan Liang,Wenlan Wu
Journal of Nanobiotechnology. 2017; 15(1)
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383 Amphiphilic small peptides for delivery of plasmid DNAs and siRNAs
Eun-Kyoung Bang,Hanna Cho,Sean S.-H. Jeon,Na Ly Tran,Dong-Kwon Lim,Wooyoung Hur,Taebo Sim
Chemical Biology & Drug Design. 2017;
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384 Transfection Studies with Colloidal Systems Containing Highly Purified Bipolar Tetraether Lipids from Sulfolobus acidocaldarius
Konrad H. Engelhardt,Shashank Reddy Pinnapireddy,Elias Baghdan,Jarmila Jedelská,Udo Bakowsky
Archaea. 2017; 2017: 1
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385 Honing Cell and Tissue Culture Conditions for Bone and Cartilage Tissue Engineering
Johnny Lam,Esther J. Lee,Elisa C. Clark,Antonios G. Mikos
Cold Spring Harbor Perspectives in Medicine. 2017; 7(12): a025734
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386 Molecular Communication and Nanonetwork for Targeted Drug Delivery: A Survey
Uche A. K. Chude-Okonkwo,Reza Malekian,B. T. Maharaj,Athanasios V. Vasilakos
IEEE Communications Surveys & Tutorials. 2017; 19(4): 3046
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387 Gene Therapy for Pancreatic Cancer: Specificity, Issues and Hopes
Marie Rouanet,Marine Lebrin,Fabian Gross,Barbara Bournet,Pierre Cordelier,Louis Buscail
International Journal of Molecular Sciences. 2017; 18(6): 1231
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388 Technical Improvement and Application of Hydrodynamic Gene Delivery in Study of Liver Diseases
Mei Huang,Rui Sun,Qiang Huang,Zhigang Tian
Frontiers in Pharmacology. 2017; 8
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389 Mesenchymal Stromal/Stem Cells: A New Era in the Cell-Based Targeted Gene Therapy of Cancer
Faroogh Marofi,Ghasem Vahedi,Alireza Biglari,Abdolreza Esmaeilzadeh,Seyyed Shamsadin Athari
Frontiers in Immunology. 2017; 8
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390 Adeno-Associated Viral Vectors Serotype 8 for Cell-Specific Delivery of Therapeutic Genes in the Central Nervous System
Diego Pignataro,Diego Sucunza,Lucia Vanrell,Esperanza Lopez-Franco,Iria G. Dopeso-Reyes,Africa Vales,Mirja Hommel,Alberto J. Rico,Jose L. Lanciego,Gloria Gonzalez-Aseguinolaza
Frontiers in Neuroanatomy. 2017; 11
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391 Magnetic nanoparticles-based drug and gene delivery systems for the treatment of pulmonary diseases
Ibrahim M El-Sherbiny,Nancy M Elbaz,Mohammed Sedki,Abdulaziz Elgammal,Magdi H Yacoub
Nanomedicine. 2017;
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392 The use of nanoparticulates to treat breast cancer
Xiaomeng Tang,Welley S Loc,Cheng Dong,Gail L Matters,Peter J Butler,Mark Kester,Craig Meyers,Yixing Jiang,James H Adair
Nanomedicine. 2017;
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393 Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy
Anish Babu,Rajagopal Ramesh
Marine Drugs. 2017; 15(4): 96
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394 An Electrostatically Self-Assembled Ternary Nanocomplex as a Non-Viral Vector for the Delivery of Plasmid DNA into Human Adipose-Derived Stem Cells
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Molecules. 2016; 21(5): 572
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395 MicroRNAs Regulate Cytokine Responses in Gingival Epithelial Cells
Steven C. Y. Chen,Christos Constantinides,Moritz Kebschull,Panos N. Papapanou,B. A. McCormick
Infection and Immunity. 2016; 84(12): 3282
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396 Therapeutic nucleic acids: current clinical status
Kannan Sridharan,Nithya Jaideep Gogtay
British Journal of Clinical Pharmacology. 2016; 82(3): 659
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397 Systematically probing the bottom-up synthesis of AuPAMAM conjugates for enhanced transfection efficiency
Elizabeth R. Figueroa,J. Stephen Yan,Nicolette K. Chamberlain-Simon,Adam Y. Lin,Aaron E. Foster,Rebekah A. Drezek
Journal of Nanobiotechnology. 2016; 14(1)
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398 Nucleic Acid Delivery for Endothelial Dysfunction in Cardiovascular Diseases
Dipti Deshpande,David R. Janero,Victor Segura-Ibarra,Elvin Blanco,Mansoor M. Amiji
Methodist DeBakey Cardiovascular Journal. 2016; 12(3): 134
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Mohmood Tavallaie
Journal of Nanotechnology and Materials Science. 2016; 3(2): 1
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400 New polymer of lactic-co-glycolic acid-modified polyethylenimine for nucleic acid delivery
Jian-Ming Lü,Zhengdong Liang,Xiaoxiao Wang,Jianhua Gu,Qizhi Yao,Changyi Chen
Nanomedicine. 2016; 11(15): 1971
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401 Improved biocompatibility and efficient labeling of neural stem cells with poly(L-lysine)-coated maghemite nanoparticles
Igor M Pongrac,Marina Dobrivojevic,Lada Brkic Ahmed,Michal Babic,Miroslav Šlouf,Daniel Horák,Srecko Gajovic
Beilstein Journal of Nanotechnology. 2016; 7: 926
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402 Significance of stem cell marker Nanog gene in the diagnosis and prognosis of lung cancer
Zeng Liu,Jing Zhang,Honggang Kang,Guiming Sun,Baozhong Wang,Yanwen Wang,Mengxiang Yang
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403 Genetic Modification of the Lung Directed Toward Treatment of Human Disease
Dolan Sondhi,Katie Stiles,Bishnu P De,Ronald G Crystal
Human Gene Therapy. 2016;
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404 Integrated Electrowetting Nanoinjector for Single Cell Transfection
Elaheh Shekaramiz,Ganeshkumar Varadarajalu,Philip J. Day,H. Kumar Wickramasinghe
Scientific Reports. 2016; 6: 29051
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405 Functional lipids based on [12]aneN3and naphthalimide as efficient non-viral gene vectors
Yong-Guang Gao,Uzair Alam,Quan Tang,You-Di Shi,Ying Zhang,Ruibing Wang,Zhong-Lin Lu
Org. Biomol. Chem.. 2016; 14(26): 6346
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406 A novel non-viral gene vector for hepatocyte-targeting and in situ monitoring of DNA delivery in single cells
Yong-Guang Gao,Quan Tang,You-Di Shi,Ying Zhang,Ruibing Wang,Zhong-Lin Lu
RSC Adv.. 2016; 6(55): 50053
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407 Nanomaterial mediated optogenetics: opportunities and challenges
Kai Huang,Qingqing Dou,Xian Jun Loh
RSC Adv.. 2016; 6(65): 60896
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408 Vascular Repair by Circumferential Cell Therapy Using Magnetic Nanoparticles and Tailored Magnets
Sarah Vosen,Sarah Rieck,Alexandra Heidsieck,Olga Mykhaylyk,Katrin Zimmermann,Wilhelm Bloch,Dietmar Eberbeck,Christian Plank,Bernhard Gleich,Alexander Pfeifer,Bernd K. Fleischmann,Daniela Wenzel
ACS Nano. 2016; 10(1): 369
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409 Effect of sustained PDGF nonviral gene delivery on repair of tooth-supporting bone defects
A B Plonka,B Khorsand,N Yu,J V Sugai,A K Salem,W V Giannobile,S Elangovan
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410 Mapping of bionic array electric field focusing in plasmid DNA-based gene electrotransfer
C J Browne,J L Pinyon,D M Housley,E N Crawford,N H Lovell,M Klugmann,G D Housley
Gene Therapy. 2016;
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411 ORMOPLEXEs for gene therapy: In vitro and in vivo assays
J.C. Matos,A.R. Soares,I. Domingues,G.A. Monteiro,M.C. Gonçalves
Materials Science and Engineering: C. 2016; 63: 546
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412 Therapeutic and diagnostic applications of extracellular vesicles
Stephan Stremersch,Stefaan C. De Smedt,Koen Raemdonck
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413 Improvement of vascular function by magnetic nanoparticle-assisted circumferential gene transfer into the native endothelium
Sarah Vosen,Sarah Rieck,Alexandra Heidsieck,Olga Mykhaylyk,Katrin Zimmermann,Christian Plank,Bernhard Gleich,Alexander Pfeifer,Bernd K. Fleischmann,Daniela Wenzel
Journal of Controlled Release. 2016;
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414 Epigenome Editing: State of the Art, Concepts, and Perspectives
Goran Kungulovski,Albert Jeltsch
Trends in Genetics. 2016; 32(2): 101
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415 Coordinative Amphiphiles as Tunable siRNA Transporters
Jin Bum Kim,Yeong Mi Lee,Jooyeon Ryu,Eunji Lee,Won Jong Kim,Gyochang Keum,Eun-Kyoung Bang
Bioconjugate Chemistry. 2016;
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416 Gene delivery using calcium phosphate nanoparticles: Optimization of the transfection process and the effects of citrate and poly(l-lysine) as additives
Mohammed A. Khan,Victoria M. Wu,Shreya Ghosh,Vuk Uskokovic
Journal of Colloid and Interface Science. 2016; 471: 48
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417 Gene transfer to the outflow tract
Yalong Dang,Ralitsa Loewen,Hardik A. Parikh,Pritha Roy,Nils A. Loewen
Experimental Eye Research. 2016;
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418 Gene based therapies for kidney regeneration
Manoe J. Janssen,Fanny O. Arcolino,Perry Schoor,Robbert Jan Kok,Enrico Mastrobattista
European Journal of Pharmacology. 2016;
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419 Micro and nanotechnologies in heart valve tissue engineering
Anwarul Hasan,John Saliba,Hassan Pezeshgi Modarres,Ahmed Bakhaty,Amir Nasajpour,Mohammad R.K. Mofrad,Amir Sanati-Nezhad
Biomaterials. 2016; 103: 278
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420 Cationic ß-Cyclodextrin–Chitosan Conjugates as Potential Carrier for pmCherry-C1 Gene Delivery
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Molecular Biotechnology. 2016; 58(4): 287
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421 Conjugates of small targeting molecules to non-viral vectors for the mediation of siRNA
Defu Zhi,Yinan Zhao,Shaohui Cui,Huiying Chen,Shubiao Zhang
Acta Biomaterialia. 2016; 36: 21
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422 Graphene-based materials for tissue engineering
Su Ryon Shin,Yi-Chen Li,HaeLin Jang,Parastoo Khoshakhlagh,Mohsen Akbari,Amir Nasajpour,Yu Shrike Zhang,Ali Tamayol,Ali Khademhosseini
Advanced Drug Delivery Reviews. 2016;
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423 Virus-inspired nucleic acid delivery system: Linking virus and viral mimicry
Rong Ni,Junli Zhou,Naushad Hossain,Ying Chau
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424 The promising alliance of anti-cancer electrochemotherapy with immunotherapy
Christophe Y. Calvet,Lluis M. Mir
Cancer and Metastasis Reviews. 2016;
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425 High-throughput screening of clinically approved drugs that prime polyethylenimine transfection reveals modulation of mitochondria dysfunction response improves gene transfer efficiencies
Albert Nguyen,Jared Beyersdorf,Jean-Jack Riethoven,Angela K. Pannier
Bioengineering & Translational Medicine. 2016;
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426 Neprilysin gene transfer: A promising therapeutic approach for Alzheimeræs disease
Yuanli Li,Junqing Wang,Shenghao Zhang,Zhaohui Liu
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427 Generation of stable cell line by using chitosan as gene delivery system
Emine Salva,Suna Özbas Turan,Ceyda Ekentok,Jülide Akbuga
Cytotechnology. 2015;
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428 Using Stem Cells to Model Diseases of the Outer Retina
Camille Yvon,Conor M. Ramsden,Amelia Lane,Michael B. Powner,Lyndon da Cruz,Peter J. Coffey,Amanda-Jayne F. Carr
Computational and Structural Biotechnology Journal. 2015; 13: 382
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429 Anticancer effect of gene/peptide co-delivery system using transferrin-grafted LMWSC
Gyeong-Won Jeong,Seong-Cheol Park,Changyong Choi,Joung-Pyo Nam,Tae-Hun Kim,Soo-Kyung Choi,Jun-Kyu Park,Jae-Woon Nah
International Journal of Pharmaceutics. 2015; 488(1-2): 165
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430 Polyamidoamine (PAMAM) dendrimers modified with short oligopeptides for early endosomal escape and enhanced gene delivery
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International Journal of Pharmaceutics. 2015; 492(1-2): 233
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431 Nanotechnology Approaches for the Delivery of Exogenous siRNA for HIV Therapy
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Molecular Pharmaceutics. 2015;
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432 Delivery of drugs and macromolecules to the mitochondria for cancer therapy
Phong Lu,Benjamin J. Bruno,Malena Rabenau,Carol S. Lim
Journal of Controlled Release. 2015;
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433 Poly(ethylenimine) conjugated bioreducible dendrimer for efficient gene delivery
Kihoon Nam,Simhyun Jung,Joung-Pyo Nam,Sung Wan Kim
Journal of Controlled Release. 2015; 220: 447
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434 Nanotechnology for mesenchymal stem cell therapies
Bruna Corradetti,Mauro Ferrari
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435 Stimuli-responsive liposomes for the delivery of nucleic acid therapeutics
Fatemeh Movahedi,Rebecca G. Hu,David L. Becker,Chenjie Xu
Nanomedicine: Nanotechnology, Biology and Medicine. 2015; 11(6): 1575
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436 A naphthalimide-based [12]aneN3compound as an effective and real-time fluorescence tracking non-viral gene vector
Yong-Guang Gao,You-Di Shi,Ying Zhang,Jing Hu,Zhong-Lin Lu,Lan He
Chem. Commun.. 2015; 51(93): 16695
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437 Highly luminescent and cytocompatible cationic Ag2S NIR-emitting quantum dots for optical imaging and gene transfection
Fatma Demir Duman,Ibrahim Hocaoglu,Deniz Gulfem Ozturk,Devrim Gozuacik,Alper Kiraz,Havva Yagci Acar
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438 Enhancement of nucleic acid delivery to hard-to-transfect human colorectal cancer cells by magnetofection at laminin coated substrates and promotion of the endosomal/lysosomal escape
María Belén Cerda,Milena Batalla,Martina Anton,Eduardo Cafferata,Osvaldo Podhajcer,Christian Plank,Olga Mykhaylyk,Lucia Policastro
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439 Synthesis of bifunctional molecules containing [12]aneN3and coumarin moieties as effective DNA condensation agents and new non-viral gene vectors
Pan Yue,Ying Zhang,Zhi-Fo Guo,Ao-Cheng Cao,Zhong-Lin Lu,Yong-Gong Zhai
Org. Biomol. Chem.. 2015; 13(15): 4494
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440 Gene therapy for ocular diseases meditated by ultrasound and microbubbles (Review)
Caifeng Wan,Fenghua Li,Hongli Li
Molecular Medicine Reports. 2015;
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441 Iron Oxide Nanoparticles Coated with a Phosphorothioate Oligonucleotide and a Cationic Peptide: Exploring Four Different Ways of Surface Functionalization
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Nanomaterials. 2015; 5(4): 1588
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442 Bacteriophages as vehicles for gene delivery into mammalian cells: prospects and problems
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Expert Opinion on Drug Delivery. 2014; : 1
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443 Gene Therapy for Inherited Muscle Diseases
Robynne Braun,Zejing Wang,David L. Mack,Martin K. Childers
American Journal of Physical Medicine & Rehabilitation. 2014; 93: S97
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444 Gene therapy in pancreatic cancer
Si-Xue Liu
World Journal of Gastroenterology. 2014; 20(37): 13343
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445 Human umbilical cord blood derived mesenchymal stem cells were differentiated into pancreatic endocrine cell by Pdx-1 electrotransfer
Phuoc Thi-My Nguyen,Anh Thai-Quynh Nguyen,Nhung Thi Nguyen,Nguyet Thi-Minh Nguyen,Thu Thi Duong,Nhung Hai Truong,Ngoc Kim Phan
Biomedical Research and Therapy. 2014; 1(2)
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446 A dual gold nanoparticle system for mesenchymal stem cell tracking
L. M. Ricles,S. Y. Nam,E. A. Treviño,S. Y. Emelianov,L. J. Suggs
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447 Advances in Lipid-Based Platforms for RNAi Therapeutics
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