A Simple Method to Increase the Transduction Efficiency of Single-Stranded Adeno-Associated Virus Vectors In Vitro and In Vivo

被引：9

作者：

Ma, Wenqin ^{[1
,2
]}

Li, Baozheng ^{[1
,2
]}

Ling, Chen ^{[1
,3
]}

Jayandharan, Giridhara R. ^{[1
,2
,6
,7
]}

Srivastava, Arun ^{[1
,2
,3
,4
,5
]}

Byrne, Barry J. ^{[1
,2
,3
,4
,5
]}

机构：

[1] Univ Florida, Coll Med, Div Cellular & Mol Therapy, Dept Pediat, Gainesville, FL 32610 USA

[2] Univ Florida, Coll Med, Powell Gene Therapy Ctr, Gainesville, FL 32610 USA

[3] Univ Florida, Coll Med, Dept Mol Biol & Microbiol, Gainesville, FL 32610 USA

[4] Univ Florida, Coll Med, Shands Canc Ctr, Gainesville, FL 32610 USA

[5] Univ Florida, Coll Med, Genet Inst, Gainesville, FL 32610 USA

[6] Christian Med Coll & Hosp, Dept Haematol, Vellore 632004, Tamil Nadu, India

[7] Christian Med Coll & Hosp, Ctr Stem Cell Res, Vellore 632004, Tamil Nadu, India

来源：

HUMAN GENE THERAPY | 2011年 / 22卷 / 05期

基金：

美国国家卫生研究院;

关键词：

2-MEDIATED GENE-TRANSFER; PROTEIN-TYROSINE-PHOSPHATASE; MILD LUNG-DISEASE; TRANSGENE EXPRESSION; FACTOR-IX; VIRAL VECTORS; AAV VECTORS; PHASE-I; PACKAGING CAPACITY; CYSTIC-FIBROSIS;

D O I：

10.1089/hum.2010.243

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

We have recently shown that co-administration of conventional single-stranded adeno-associated virus 2 (ssAAV2) vectors with self-complementary (sc) AAV2-protein phosphatase 5 (PP5) vectors leads to a significant increase in the transduction efficiency of ssAAV2 vectors in human cells in vitro as well as in murine hepatocytes in vivo. In the present study, this strategy has been further optimized by generating a mixed population of ssAAV2-EGFP and scAAV2-PP5 vectors at a 10: 1 ratio to achieve enhanced green fluorescent protein (EGFP) transgene expression at approximately 5- to 10-fold higher efficiency, both in vitro and in vivo. This simple coproduction method should be adaptable to any ssAAV serotype vector containing transgene cassettes that are too large to be encapsidated in scAAV vectors.

引用

页码：633 / 640

页数：8

共 38 条

[1] A phase I study of aerosolized administration of tgAAVCF to cystic fibrosis subjects with mild lung disease [J].