High-efficiency transduction of human monocyte-derived dendritic cells by capsid-modified recombinant AAV2 vectors.
High-efficiency transduction of human monocyte-derived dendritic cells by capsid-modified recombinant AAV2 vectors.
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DOI：
10.1016/j.vaccine.2012.03.079
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发表时间：
2012-06-06
期刊：
影响因子：
5.5
通讯作者：
Srivastava, Arun
中科院分区：
文献类型：
--
作者：
Aslanidi, George V.;Rivers, Angela E.;Ortiz, Luis;Govindasamy, Lakshmanan;Ling, Chen;Jayandharan, Giridhara R.;Zolotukhin, Sergei;Agbandje-McKenna, Mavis;Srivastava, Arun
关键词：
Phosphorylation of surface-exposed tyrosine residues negatively impacts the transduction efficiency of recombinant AAV2 vectors. Pre-treatment of cells with specific cellular serine/threonine kinase inhibitors also significantly increased the transduction efficiency of AAV2 vectors. We reasoned that site-directed mutagenesis of surface-exposed serine residues might allow the vectors to evade phosphorylation and thus lead to higher transduction efficiency. Each of the 15 surface-exposed serine (S) residues was substituted with valine (V) residues, and the transduction efficiency of three of these mutants, S458V, S492Vand S662V, was increased by up to∼20-fold in different cell types. The S662V mutant was efficient in transducing human monocyte-derived dendritic cells (moDCs), a cell type not readily amenable to transduction by the conventional AAV vectors, and did not induce any phenotypic changes in these cells. Recombinant S662V-AAV2 vectors encoding a truncated human telomerase (hTERT) gene were generated and used to stimulate cytotoxic T cells (CTLs) against target cells. S662V-AAV2-hTERT vector-transduced DCs resulted in rapid, specific T-cell clone proliferation and generation of robust CTLs, which led to specific cell lysis of K562 cells. These studies suggest that high-efficiency transduction of moDCs by serine-modified AAV2 vectors is feasible, which supports the potential utility of these vectors for future human DC vaccine studies.
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影响因子：
5.8
作者：
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通讯作者：
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DOI：
10.1073/pnas.0810614106
发表时间：
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影响因子：
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影响因子：
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作者：
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