| RRC ID |
51847
|
| 著者 |
Tabata K, Sugano E, Murakami F, Yamashita T, Ozaki T, Tomita H.
|
| タイトル |
Improved transduction efficiencies of adeno-associated virus vectors by synthetic cell-permeable peptides.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| 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.
|
| 巻・号 |
478(4)
|
| ページ |
1732-8
|
| 公開日 |
2016-9-30
|
| DOI |
10.1016/j.bbrc.2016.09.014
|
| PII |
S0006-291X(16)31464-4
|
| PMID |
27614311
|
| MeSH |
Amino Acid Sequence
Animals
Blotting, Western
Cell Line
Cell-Penetrating Peptides / chemical synthesis
Cell-Penetrating Peptides / pharmacology*
Dependovirus / genetics*
Dose-Response Relationship, Drug
Embryo, Mammalian / cytology
Fibroblasts / cytology
Fibroblasts / drug effects*
Fibroblasts / metabolism
Genetic Vectors / genetics
Macaca fascicularis
Microscopy, Fluorescence
Phosphorylation / drug effects
Rats
Reproducibility of Results
Skin / cytology
Skin / drug effects*
Skin / metabolism
Transduction, Genetic / methods*
p38 Mitogen-Activated Protein Kinases / metabolism
|
| IF |
2.985
|
| 引用数 |
1
|
| リソース情報 |
| ヒト・動物細胞 |
CYNOM-K1(RCB0471) |
