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Improved transduction efficiencies of adeno-associated virus vectors by synthetic cell-permeable peptides.

Improved transduction efficiencies of adeno-associated virus vectors by synthetic cell-permeable peptides.
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Tabata K, Sugano E, Murakami F, Yamashita T, Ozaki T, Tomita H,


Tabata K, Sugano E, Murakami F, Yamashita T, Ozaki T, Tomita H, (click to view)

Tabata K, Sugano E, Murakami F, Yamashita T, Ozaki T, Tomita H,

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Biochemical and biophysical research communications 2016 9 7() pii 10.1016/j.bbrc.2016.09.014

Abstract

Various serotypes of adeno-associated virus (AAV) vectors have been used for gene therapy and as research tools. Among these serotypes, the AAV type 2 vector has been used successfully in human gene therapies. However, the transduction efficiency of AAV2 depends on the cell type, and this poses a problem in the efficacy of gene therapy. To improve the transduction efficiency of AAV2, we designed a small peptide consisting of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor peptide and the HIV-Tat sequence Tat-Y1068. Pre- or co-treatment of CYNOM-K1 cells from cynomolgus monkey embryo skin with Tat-Y1068 increased the transduction efficiencies in a dose-dependent manner and caused p38 phosphorylation. The transduction efficiency of AAV2 into the rat fibroblast cell line RAT-1 highly expressing EGFR was less than the transduction efficiency of AAV2 into CYNOM-K1 cells. Tat-Y1068 increased the transduction efficiency in RAT-1 cells in the same manner as in CYNOM-K1 cells. In conclusion, cell-permeable peptides possessing the EGFR tyrosine kinase inhibitor function might serve as a useful ingredient of AAV2 vector solution for increasing the transduction efficiency of gene therapies.

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