AAV2 Gene Therapy Readministration in Three Adults with Congenital Blindness

被引：313

作者：

Bennett, Jean ^{[1
,2
]}

Ashtari, Manzar ^{[3
]}

Wellman, Jennifer ^{[2
]}

Marshall, Kathleen A. ^{[2
]}

Cyckowski, Laura L. ^{[3
]}

Chung, Daniel C. ^{[1
,2
]}

McCague, Sarah ^{[2
]}

Pierce, Eric A. ^{[1
,4
]}

Chen, Yifeng ^{[2
]}

Bennicelli, Jeannette L. ^{[1
]}

Zhu, Xiaosong ^{[4
]}

Ying, Gui-shuang ^{[5
]}

Sun, Junwei ^{[2
]}

Wright, J. Fraser ^{[2
]}

Auricchio, Alberto ^{[6
,7
]}

Simonelli, Francesca ^{[6
,8
]}

Shindler, Kenneth S. ^{[1
]}

Mingozzi, Federico ^{[2
]}

High, Katherine A. ^{[2
,9
]}

Maguire, Albert M. ^{[1
,2
,4
]}

机构：

[1] Univ Penn, FM Kirby Ctr Mol Ophthalmol, Scheie Eye Inst, Philadelphia, PA 19104 USA

[2] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA 19104 USA

[3] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA

[4] Childrens Hosp Philadelphia, Dept Ophthalmol, Philadelphia, PA 19104 USA

[5] Univ Penn, Ctr Prevent Ophthalmol & Biostat, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA

[6] Telethon Inst Genet & Med, I-80131 Naples, Italy

[7] Univ Naples Federico 2, Dept Pediat, I-80131 Naples, Italy

[8] Univ Naples 2, Dept Ophthalmol, I-80131 Naples, Italy

[9] Univ Penn, Howard Hughes Med Inst, Philadelphia, PA 19104 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2012年 / 4卷 / 120期

关键词：

ADENOASSOCIATED VIRUS; RPE65; MUTATIONS; CHILDHOOD BLINDNESS; CANINE MODEL; VISUAL CYCLE; AMAUROSIS; VISION; ROD; DYSTROPHY; RETINA;

D O I：

10.1126/scitranslmed.3002865

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Demonstration of safe and stable reversal of blindness after a single unilateral subretinal injection of a recombinant adeno-associated virus (AAV) carrying the RPE65 gene (AAV2-hRPE65v2) prompted us to determine whether it was possible to obtain additional benefit through a second administration of the AAV vector to the contralateral eye. Readministration of vector to the second eye was carried out in three adults with Leber congenital amaurosis due to mutations in the RPE65 gene 1.7 to 3.3 years after they had received their initial subretinal injection of AAV2-hRPE65v2. Results (through 6 months) including evaluations of immune response, retinal and visual function testing, and functional magnetic resonance imaging indicate that readministration is both safe and efficacious after previous exposure to AAV2-hRPE65v2.

引用

页数：10

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