Barriers to Nonviral Gene Delivery

Wiethoff, Christopher M.; Middaugh, C. Russell

doi:10.1002/jps.10286

Cited by 444 publications

(348 citation statements)

References 142 publications

(178 reference statements)

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“…Nonviral gene delivery approaches differ from the use of viral vectors in that they not only are less toxic, less immunogenic, and less costly to produce, but also suffer from being less efficient in gene delivery [3,4]. Nonviral gene complexes typically consist of circular, plasmid DNA, which is highly negatively charged, electrostatically complexed with cationic lipids or polymers to form lipoplex and polyplex DNA-nanoparticles (DNA-NPs), respectively [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Dynamic analysis of DNA nanoparticle immobilization to model biomaterial substrates using combinatorial spectroscopic ellipsometry and quartz crystal microbalance with dissipation

et al. 2014

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Section: Introductionmentioning

confidence: 99%

Dynamic analysis of DNA nanoparticle immobilization to model biomaterial substrates using combinatorial spectroscopic ellipsometry and quartz crystal microbalance with dissipation

et al. 2014

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“…Therefore, several strategies have been developed to overcome barriers to non-viral gene delivery and to enhance transfection efficacies [14,15]. The use of cationic polymers or lipoplexes and other reagents for non-viral gene delivery is a well established method which can significantly increase transfection efficacies in vitro and in vivo [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of fibrin-based gene-activated matrices for BMP2/7 plasmid codelivery in a rat nonunion model

Kaipel

Schützenberger

Hofmann

et al. 2014

International Orthopaedics (SICOT)

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PURPOSE: Treatment of large segmental bone defects still is a challenge in clinical routine.Application of Gene-activated matrices (GAMs) based on fibrin, BMP 2/7 plasmids and nonviral transfection reagents (cationic polymers) could be an innovative treatment strategy to overcome this problem.The aim of this study was to determine the therapeutic efficacy of fibrin GAMs with or without additional transfection reagents for bone morphogenic protein (BMP)2 and BMP7 plasmid co-delivery in a rat femur non-union model. METHODS:In this experimental study a critical size femoral defect was created in 27 rats. At 4 weeks after the surgery animals were separated into 4 groups and underwent a second operation. Fibrin clots containing BMP2 and BMP7 plasmids with and without cationic polymer were implanted into the femoral defect. Fibrin clots containing recombinant human (rh) BMP2 served as positive and clots without supplement as negative controls.RESULTS: At 8 weeks animals which received GAMs containing the cationic polymer and BMP 2/7 plasmids showed decreased bone volume compared to animals treated with GAMs and BMP2/7 only. Application of BMP2 and BMP7 plasmids in fibrin GAMs without cationic polymer lead to variable results. Animals which received rhBMP 2 protein showed increased bone volume and osseous unions were achieved in 2 out of 6 animals.2 CONCLUSIONS: Cationic polymers decrease therapeutic efficiency of fibrin GAM based BMP2/7 plasmid co-delivery in bone regeneration. Non-viral gene transfer of BMP2/7 plasmids needs alternative promoters (e.g. by sonoporation, electroporation) to promise beneficial clinical effects.

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“…Non-viral vectors, such as cationic lipids, polymers, dendrimers and peptides, have recently attracted a great deal of attention because of their ease in preparation, flexibility in the size of the transgene and biocompatibility. [1][2][3][4] Polyethyleneimine (PEI) is a polymeric non-viral vector that has shown promise to effectively condense nucleic acids into nanosize particles, facilitate their escape from endosomal compartments and mediate gene expression in a variety of mammalian cells. [5][6][7] The endosomolytic activity of PEI is proportional to its molecular weight and, as it increases, the ability to lyse endosomes increases.…”

Section: Introductionmentioning

confidence: 99%

Modified polyethyleneimine with histidine–lysine short peptides as gene carrier

et al. 2010

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There are several strategies that can be utilized to improve transfection efficiency while reducing the cytotoxicity of polyethyleneimine (PEI) as a promising non-viral gene delivery vector. In this study, we evaluated the potential use of lysinehistidine (KH) peptides in modifying the PEI 10 kDa structure and enhancing its efficiency while maintaining low toxicity of PEI. PEI 10 kDa was modified with 6-bromohexanoic acid (alkyl) to increase its lipophilicity. Then, ethylenediamine (EDA) was attached to the carboxylic groups of PEI-hexanoate to restore the primary amines of PEI. Subsequently, six different KH short peptides were conjugated to PEIs and evaluated for the effect of the KH sequence on vector transfection efficiency and cytotoxicity. The transfection efficiency of PEI-peptides complexed with a luciferase reporter gene (pRLCMV) in Neuro-2A murine neuroblastoma cells showed that the PEI conjugated to KHHHKKHHHK peptide had a significantly higher rate of gene transfection efficiency in comparison with other KH peptides. This peptide was conjugated to PEI-alkyl and PEI-alkyl-EDA and significant improvement in efficiency with minimal cytotoxicity was observed. The results obtained suggest that the sequence and content of KH peptides will have a significant impact on the transfection efficiency of modified PEI 10 kDa.

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Barriers to Nonviral Gene Delivery

Cited by 444 publications

References 142 publications

Dynamic analysis of DNA nanoparticle immobilization to model biomaterial substrates using combinatorial spectroscopic ellipsometry and quartz crystal microbalance with dissipation

Dynamic analysis of DNA nanoparticle immobilization to model biomaterial substrates using combinatorial spectroscopic ellipsometry and quartz crystal microbalance with dissipation

Evaluation of fibrin-based gene-activated matrices for BMP2/7 plasmid codelivery in a rat nonunion model

Modified polyethyleneimine with histidine–lysine short peptides as gene carrier

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