High-Density Recombinant Adeno-Associated Viral Particles are Competent Vectors for In Vivo Transduction

被引：13

作者：

Wang, Qizhao ^{[1
,2
]}

Firrman, Jenni ^{[3
,6
]}

Wu, Zhongren ^{[2
]}

Pokiniewski, Katie A. ^{[3
]}

Valencia, C. Alexander ^{[7
,8
]}

Wang, Hairong ^{[4
]}

Wei, Hongying ^{[2
]}

Zhuang, Zhenjing ^{[1
,2
]}

Liu, LinShu ^{[6
]}

Wunder, Stephanie L. ^{[4
]}

Chin, Mario P. S. ^{[1
]}

Xu, Ruian ^{[1
]}

Diao, Yong ^{[1
]}

Dong, Biao ^{[2
]}

Xiao, Weidong ^{[1
,2
,3
,5
,6
]}

机构：

[1] Huaqiao Univ, Inst Genom, Sch Biomed Sci, Quanzhou, Peoples R China

[2] Temple Univ, Sol Sherry Thrombosis Res Ctr, Philadelphia, PA 19122 USA

[3] Temple Univ, Dept Microbiol & Immunol, Philadelphia, PA 19140 USA

[4] Temple Univ, Dept Chem, Philadelphia, PA 19122 USA

[5] Temple Univ, Cardiovasc Res Ctr, Philadelphia, PA 19122 USA

[6] ARS, USDA, ERRC, Wyndmoor, PA USA

[7] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA

[8] Univ Cincinnati, Sch Med, Dept Pediat, Cincinnati, OH USA

来源：

HUMAN GENE THERAPY | 2016年 / 27卷 / 12期

基金：

美国国家科学基金会;

关键词：

AAV; density; gene therapy; capsid; HUMAN GENE-THERAPY; CLINICAL-TRIAL; HEMOPHILIA-B; VIRUS TYPE-2; MRE11/RAD50/NBS1; COMPLEX; HUMORAL IMMUNITY; LIGHT PARTICLES; CAPSID PROTEIN; AAV VECTORS; INFECTIVITY;

D O I：

10.1089/hum.2016.055

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：

Recombinant adeno-associated viral (rAAV) vectors have recently achieved clinical successes in human gene therapy. However, the commonly observed, heavier particles found in rAAV preparations have traditionally been ignored due to their reported low in vitro transduction efficiency. In this study, the biological properties of regular and high-density rAAV serotype 8 vectors, rAAV(RD) and rAAV(HD), were systemically compared. Results demonstrated that both rAAV(RD) and rAAV(HD) exhibited similar DNA packaging profiles, while rAAV(HD) capsids contained fewer VP1 and VP2 proteins, indicating that the rAAV(HD) particles contained a higher DNA/protein ratio than that of rAAV(RD) particles. Dynamic light scattering and transmission electron microscopy data revealed that the diameter of rAAV(HD) was smaller than that of rAAV(RD). In vitro, rAAV(HD) was two-to fourfold less efficient in transduction compared with rAAV(RD). However, the transduction performance of rAAV(HD) and rAAV(RD) was similar in vivo. No significant difference in neutralizing antibody formation against rAAV(RD) and rAAV(HD) was observed, suggesting that the surface epitopes of rAAV(RD) and rAAV(HD) are congruent. In summary, the results of this study demonstrate that rAAV(RD) and rAAV(HD) are equally competent for in vivo transduction, despite their difference in vitro. Therefore, the use of rAAV(HD) vectors in human gene therapy should be further evaluated.

引用

页码：971 / 981

页数：11

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