Water-soluble lipopolymer as a gene carrier to corpus cavernosum

Lee, M.; Ryu, Ji‐Kan; Oh, Seung Min; Lee, E.; Shin, Hwa Yean; Song, Sun U.; Kim, S. W.; Suh, Jun‐Kyu

doi:10.1038/sj.ijir.3901314

Cited by 22 publications

(17 citation statements)

References 32 publications

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“…pCMV-Luc, the GBP/pCMV-Luc polyplexes (weight ratio: 20, 40, 60 and 80) or the PEI25K/pCMV-Luc polyplex (weight ratio = 1) was injected into the midportion of the corpus cavernosum of the hypercholesterolaemic mice (N = 5 per group), and the needle was left in place for 2 min to allow the gene to diffuse throughout the cavernous space as previously described (Lee et al, 2005). The amount of pCMV-Luc was fixed at 0.5 lg per each polyplex.…”

Section: Cytotoxicitymentioning

confidence: 99%

A guanidinylated bioreducible polymer as a novel gene carrier to the corpus cavernosum of mice with high‐cholesterol diet‐induced erectile dysfunction

et al. 2013

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SUMMARYA prerequisite for the successful clinical application of gene therapy in erectile dysfunction (ED) is the availability of safe and efficient gene delivery systems. The aim of this study was to examine the effectiveness of guanidinylated bioreducible polymer (GBP) polyplexes for gene delivery systems, which take advantage of the biodegradability of reducible disulfide bonds and the cell-penetrating ability of guanidine groups. For in vitro transfection experiments, we used mouse cavernous endothelial cells and A7r5 rat vascular smooth muscle cells. For in vivo experiments, we used a mouse model of hypercholesterolaemic ED in which 2-month-old male C57BL/6 mice were fed a diet containing 4% cholesterol and 1% cholic acid for 3 months. Animals or cells were treated with pCMVLuc, poly(ethyleneimine) (PEI)25k/pCMV-Luc polyplex (weight ratio: 1) and GBP/pCMV-Luc polyplexes (weight ratio: 20, 40, 60 and 80). Gene expression was evaluated by luciferase assay, and the gene expression area was evaluated by immunohistochemistry. GBP had greater transfection efficiency as the weight ratio increased. GBP had sevenfold higher gene delivery efficiency in A7r5 cells at a weight ratio of 80 than did PEI25k. Moreover, the gene expression was more profoundly induced by GBP/pCMV-Luc than by pCMVLuc in both the corpus cavernosum tissue of hypercholesterolaemic mice and in mouse cavernous endothelial cells, although the expression levels induced by the GBP gene delivery system were lower than those induced by the PEI25k gene delivery system. GBP revealed no considerable cytotoxicity to A7r5 cells and mouse cavernous endothelial cells (relative cell viability: 95 and 88% respectively), whereas PEI25k resulted in high cytotoxicity. Interestingly, immunofluorescent double staining revealed that luciferase expression induced by the GBP polyplex mainly overlapped with cavernous endothelial cells, but rarely with smooth muscle cells. The GBP-based non-viral gene expression system may be useful for the development of gene therapy in vasculogenic ED.

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Section: Cytotoxicitymentioning

confidence: 99%

A guanidinylated bioreducible polymer as a novel gene carrier to the corpus cavernosum of mice with high‐cholesterol diet‐induced erectile dysfunction

et al. 2013

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“…9 It exists in either branched or linear forms and has undergone many modifications by various investigators to increase solubility, half-life, cellular uptake and nuclear delivery while decreasing cytotoxicity. 10,11 The optimal formulation for a given application appears to be dependent on the specific target tissue.…”

Section: Introductionmentioning

confidence: 99%

Vascular endothelial growth factor (VEGF) gene therapy using a nonviral gene delivery system improves erectile function in a diabetic rat model

Dall’Era¹,

Meacham²,

Mills³

et al. 2008

Int J Impot Res

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Erectile dysfunction (ED) is a cause of decreased quality of life in more than 70% of diabetic men. Vascular endothelial growth factor (VEGF) has shown to improve overall endothelial and smooth muscle cell dysfunction in models of ED. We describe a novel technique for nonviral, in vivo gene transfection of VEGF in the rat corpus cavernosum. Diabetic rats were transfected with DNA encoding a fusion VEGF/green fluorescent protein (GFP) complex and fluorescence microscopy was used to monitor the expression of VEGF-GFP fusion protein. Western blot and PCR analyses confirmed the expression of the GFP-VEGF fusion protein and mRNA. Functional studies using cavernous nerve stimulation revealed maximal intracavernous pressures (ICPs) of 63.1 mm Hg, and 30.7 mm Hg in the normal and diabetic control groups, respectively, and 47.4 mm Hg in VEGF-GFPtransfected diabetic group. Immunohistochemical analysis of the cavernosal tissue from transfected rats showed increased smooth muscle content compared with the diabetic control group. We show for the first time in our animal model that expression of the transfected VEGF in cavernosal tissue leads to an overall improvement of maximal ICP and smooth muscle content. On the basis of these results, it is tempting to speculate that our nonviral vector system offers an excellent system for gene delivery into cavernosal tissue, and that VEGF gene therapy using this system could be useful in improving erectile function in diabetic men.

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“…The use of this polymer has been used to deliver genes to several different cancers, myocardium and corpus cavernosum. [45][46][47][48][49] In summary, we have demonstrated that ischemiainducible VEGF gene therapy improves the efficacy of VEGF gene therapy for myocardial infarction through decreased apoptosis and increased angiogenesis.…”

Section: Ischemia-inducible Gene Therapy Jw Yockman Et Almentioning

confidence: 89%

Polymeric gene delivery of ischemia-inducible VEGF significantly attenuates infarct size and apoptosis following myocardial infarct

et al. 2008

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Water-soluble lipopolymer as a gene carrier to corpus cavernosum

Cited by 22 publications

References 32 publications

A guanidinylated bioreducible polymer as a novel gene carrier to the corpus cavernosum of mice with high‐cholesterol diet‐induced erectile dysfunction

A guanidinylated bioreducible polymer as a novel gene carrier to the corpus cavernosum of mice with high‐cholesterol diet‐induced erectile dysfunction

Vascular endothelial growth factor (VEGF) gene therapy using a nonviral gene delivery system improves erectile function in a diabetic rat model

Polymeric gene delivery of ischemia-inducible VEGF significantly attenuates infarct size and apoptosis following myocardial infarct

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