TY  - JOUR
JF  - Human Molecular Genetics
UR  - http://dx.doi.org/10.1093/hmg/ddr218
EP  -  3175
TI  - Long-term and age-dependent restoration of visual function in a mouse model of CNGB3-associated achromatopsia following gene therapy
SP  - 3161 
KW  - nucleotide-gated channel
KW  -  leber congenital amaurosis
KW  -  cone photoreceptor
KW  -  adenoassociated-virus
KW  -  retinitis-pigmentosa
KW  -  CNGA3 mutations
KW  -  color-blindness
KW  -  transgenic mice
KW  -  restores vision
KW  -  alpha-subunit
AV  - public
VL  - 20
N2  - Mutations in the CNGB3 gene account for > 50% of all known cases of achromatopsia. Although of early onset, its stationary character and the potential for rapid assessment of restoration of retinal function following therapy renders achromatopsia a very attractive candidate for gene therapy. Here we tested the efficacy of an rAAV2/8 vector containing a human cone arrestin promoter and a human CNGB3 cDNA in CNGB3 deficient mice. Following subretinal delivery of the vector, CNGB3 was detected in both M-and S-cones and resulted in increased levels of CNGA3, increased cone density and survival, improved cone outer segment structure and normal subcellular compartmentalization of cone opsins. Therapy also resulted in long-term improvement of retinal function, with restoration of cone ERG amplitudes of up to 90% of wild-type and a significant improvement in visual acuity. Remarkably, successful restoration of cone function was observed even when treatment was initiated at 6 months of age; however, restoration of normal visual acuity was only possible in younger animals (e.g. 2-4 weeks old). This study represents achievement of the most substantial restoration of visual function reported to date in an animal model of achromatopsia using a human gene construct, which has the potential to be utilized in clinical trials.
Y1  - 2011/08/15/
ID  - discovery1307698
SN  - 0964-6906
A1  - Carvalho, LS
A1  - Xu, JH
A1  - Pearson, RA
A1  - Smith, AJ
A1  - Bainbridge, JW
A1  - Morris, LM
A1  - Fliesler, SJ
A1  - Ding, XQ
A1  - Ali, RR
PB  - OXFORD UNIV PRESS
N1  - This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is
properly cited.
IS  - 16
ER  -