AAV2 gene therapy readministration in three adults with congenital blindness.
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.
F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 309 Stellar-Chance Labs, 422 Curie Boulevard, Philadelphia, PA 19104, USA. jebennet@mail.med.upenn.edu
Jean
J
Bennett
Manzar
M
Ashtari
Jennifer
J
Wellman
Kathleen A
KA
Marshall
Laura L
LL
Cyckowski
Daniel C
DC
Chung
Sarah
S
McCague
Eric A
EA
Pierce
Yifeng
Y
Chen
Jeannette L
JL
Bennicelli
Xiaosong
X
Zhu
Gui-Shuang
GS
Ying
Junwei
J
Sun
J Fraser
JF
Wright
Alberto
A
Auricchio
Francesca
F
Simonelli
Kenneth S
KS
Shindler
Federico
F
Mingozzi
Katherine A
KA
High
Albert M
AM
Maguire
D000328:Adult; D001766:Blindness / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D019745:cis-trans-Isomerases / Q000235:genetics / Q000378:metabolism; D000099178:Retinoid Isomerohydrolase
D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase