Non-ionic amphiphilic biodegradable PEG–PLGA–PEG copolymer enhances gene delivery efficiency in rat skeletal muscle

Chang, Chia-Wei; Choi, Donghoon; Kim, Won Jong; Yockman, James W.; Christensen, Lane V.; Kim, Yong Hee; Kim, Sung Wan

doi:10.1016/j.jconrel.2006.11.025

Cited by 62 publications

(48 citation statements)

References 46 publications

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“…[36][37][38] The most successful cases occur after intranasal or intratracheal administration, when targeting airway epithelial cells. 3,5,9,39 Tissues containing nondividing cells (as in muscle) or slow mitotic cells (as in the liver) are very attractive targets because pDNA can remain for a long time inside the cells.…”

Section: Discussionmentioning

confidence: 99%

“…7,39 Furthermore, Brooks et al saw a dose-dependent silencing of the expression of the transgene: the higher the initial gene expression the quicker it was silenced. 41 In the study by Chang et al, 38 pDNA was formulated with the block copolymer, PEG-PLGA-PEG.The resulting pDNA complexes induced a significant increase in luciferase expression by threefold, as compared with naked DNA. On the contrary, pDNA complexed with these short lipospermines increased luciferase activity by a factor of 10 over that of naked pDNA.…”

Section: Discussionmentioning

confidence: 99%

“…34,42,43 Similar to these, as well as to other vehicles, in vitro transfection activity of lipospermines was poor (data not shown). 38,42 Delivery systems that are efficient in the skeletal muscle or skin may be used for the purpose of DNA vaccine development. In addition, in the muscle, they can also be important for the treatment of disorders caused by the lack of an active protein, which has a systemic effect and can be produced in the muscle and thereafter secreted; for example, the Anderson-Fabry disease.…”

Section: Discussionmentioning

confidence: 99%

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Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

et al. 2009

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The lack of efficient in vivo gene delivery is a well-known shortcoming of nonviral delivery vectors, in particular of chemical vectors. We developed a series of novel nonviral carriers for plasmid-based in vivo gene delivery. This new transport device is based on the assembly of DNA plasmids with synthetic derivatives of naturally occurring moleculesfatty acid-spermine conjugates (or lipospermines). We tested the ability of these fatty acid conjugates to interact with plasmid DNA (pDNA) and found that they formed DNA nanocomplexes, which are protected from DNase I degradation. This protection was shown to directly correlate with the length of the aliphatic component. However, this increase in the length of the hydrocarbon chain resulted in increased toxicity. The cationic lipids used for transfection typically have a C 16 and C 18 hydrocarbon chain. Interestingly, toxicity studies, together with further characterization studies, suggested that the two most suitable candidates for in vivo delivery are those with the shortest hydrocarbon chain, butanoyl-and decanoylspermine. Morphological characterization of DNA nanocomplexes resulting from these lipospermines showed the formation of a homogenous population, with the diameter ranging approximately from 40 to 200 nm. Butanoylspermine was found to be the most promising carrier from this series, resulting in a significantly increased gene expression, in relation to naked plasmid, in both tissues herein targeted (dermis and M. tibialis anterior). Thus, we established a correlation between the in vitro properties of the ensuing DNA nanocarriers and their efficient in vivo gene expression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

et al. 2009

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“…The first approach is to increase the efficiency of pDNA delivery. These methods include (1) chemical methods such as polymer-based carrier mediated pDNA delivery [9,10]; (2) physical methods such as electroporation [11,12] or ultrasound microbubble-mediated pDNA delivery [13]. The second approach is to optimize the transgene expression cassette by testing different transcription/translation regulatory elements such as promoter [14,15], enhancer [16,17] and 3′ untranslated region [18,19].…”

Section: Introductionmentioning

confidence: 99%

Efficient expression of vascular endothelial growth factor using minicircle DNA for angiogenic gene therapy

Chang

Christensen

Lee

et al. 2008

Journal of Controlled Release

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The application of plasmid DNA (pDNA)-based gene therapy is limited by its inefficient transgene expression. In this study, minicircle DNA was evaluated for efficient vascular endothelial growth factor (VEGF) expression in skeletal muscle cells. Production of minicircle DNA encoding VEGF was studied by a semi-quantitative electrophoresis method leading to optimized bacterial culture conditions and producing high purity (86.6 %) minicircle DNA. The VEGF minicircle DNA under control of the SV40 promoter (pMini-SV-VEGF) showed an increased amount of VEGF mRNA and up to 8 times more VEGF expression than a conventional plasmid (pSV-VEGF) in two different skeletal muscle cell lines (C2C12 and L8). Minicircle DNA with different promoters, including the SV40, CMV and chicken β-actin, was tested for VEGF expression in a C2C12 skeletal muscle cell line. The high VEGF expression generated by minicircle DNA stimulated efficient endothelial cell growth in vitro. Furthermore, minicircle DNA expressed higher VEGF compared to conventional plasmid in the tibialis anterior (TA) muscle of mice. Taken together, the results suggest that minicircle DNA is an efficacious gene vector for angiogenic VEGF expression in skeletal muscle and may be useful for treating peripheral arterial disease (PAD).

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“…In an effort to improve the efficiency of nucleic acid delivery without compromising carrier induced toxicity, researchers have proposed novel approaches. Hydrolyzable polyesters, for example, comprise a major class of biodegradable polymeric gene carriers including linear and hyperbranched poly(ester amine)s [4][5][6][7][8], poly[α-(4-aminobutyl)-L-glycolic acid [9], multiblock copolymers of poly(L-lysine) and poly(ethylene glycol) [10,11], nonionic poly (ethylene glycol) and poly(lactic-co-glycolic) copolymers [12,13], and degradable polyethylenimine (PEI) [14][15][16]. Acid labile cationic polymers through Schiff base formation [17] and polyphosphazines [18] have also been looked at.…”

Section: Introductionmentioning

confidence: 99%

Reducible poly(amido ethylenediamine) for hypoxia-inducible VEGF delivery

Christensen

Chang

Yockman

et al. 2007

Journal of Controlled Release

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Delivery of the hypoxia inducible vascular endothelial growth factor (RTP-VEGF) plasmid using a novel reducible disulfide poly(amido ethylenediamine) (SS-PAED) polymer carrier was studied in vitro and in vivo. In vitro transfection of primary rat cardiomyoblasts (H9C2) showed SS-PAED at a weighted ratio of 12:1 (polymer/DNA) mediates 16 fold higher expression of luciferase compared to an optimized bPEI control. FACS analysis revealed up to 57 ± 2% GFP positive H9C2s. The efficiency of plasmid delivery to H9C2 using SS-PAED was found to depend upon glutathione (GSH) levels inside the cell. SS-PAED mediated delivery of RTP-VEGF plasmid produced significantly higher levels of VEGF expression (up to 76 fold) under hypoxic conditions compared to normoxic conditions in both H9C2 and rat aortic smooth muscle cells (A7R5). Using SS-PAED, delivery of RTP-VEGF was investigated in a rabbit myocardial infarct model using 100 μg RTP-VEGF. Results showed up to 4 fold increase in VEGF protein expression in the region of the infarct compared to injections of SS-PAED/RTP-Luc. In conclusion, SS-PAED mediated therapeutic delivery improves the efficacy of ischemia-inducible VEGF gene therapy both in vitro and in vivo and therefore, has potential for the promotion of neo-vascular formation and improvement of tissue function in ischemic myocardium.

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Non-ionic amphiphilic biodegradable PEG–PLGA–PEG copolymer enhances gene delivery efficiency in rat skeletal muscle

Cited by 62 publications

References 46 publications

Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

Efficient expression of vascular endothelial growth factor using minicircle DNA for angiogenic gene therapy

Reducible poly(amido ethylenediamine) for hypoxia-inducible VEGF delivery

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