Gene therapy in the second eye of RPE65-deficient dogs improves retinal function

被引：56

作者：

Annear, M. J. ^{[1
]}

Bartoe, J. T. ^{[1
]}

Barker, S. E. ^{[2
]}

Smith, A. J. ^{[2
]}

Curran, P. G. ^{[3
]}

Bainbridge, J. W. ^{[2
]}

Ali, R. R. ^{[2
]}

Petersen-Jones, S. M. ^{[1
]}

机构：

[1] Michigan State Univ, Dept Small Anim Clin Sci, E Lansing, MI 48824 USA

[2] UCL, Inst Ophthalmol, Dept Genet, London, England

[3] Michigan State Univ, Ctr Stat Consulting, E Lansing, MI 48824 USA

来源：

GENE THERAPY | 2011年 / 18卷 / 01期

关键词：

rAAV2; Leber congenital amaurosis; RPE65; canine model; immune response; repeated injection; ADENOASSOCIATED VIRUS VECTORS; LEBERS CONGENITAL AMAUROSIS; OCULAR SUBRETINAL INJECTION; CANINE MODEL; IMMUNE-RESPONSES; CHILDHOOD BLINDNESS; RPE65-/-DOGS; MOUSE LUNG; PHASE-I; TRANSDUCTION;

D O I：

10.1038/gt.2010.111

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The purpose of this study was to evaluate whether immune responses interfered with gene therapy rescue using subretinally delivered recombinant adeno-associated viral vector serotype 2 carrying the RPE65 cDNA gene driven by the human RPE65 promoter (rAAV2.hRPE65p.hRPE65) in the second eye of RPE65-/- dogs that had previously been treated in a similar manner in the other eye. Bilateral subretinal injection was performed in nine dogs with the second eye treated 85-180 days after the first. Electroretinography (ERG) and vision testing showed rescue in 16 of 18 treated eyes, with no significant difference between first and second treated eyes. A serum neutralizing antibody (NAb) response to rAAV2 was detected in all treated animals, but this did not prevent or reduce the effectiveness of rescue in the second treated eye. We conclude that successful rescue using subretinal rAAV2.hRPE65p.hRPE65 gene therapy in the second eye is not precluded by prior gene therapy in the contralateral eye of the RPE65-/- dog. This finding has important implications for the treatment of human LCA type II patients. Gene Therapy (2011) 18, 53-61; doi: 10.1038/gt.2010.111; published online 12 August 2010

引用

页码：53 / 61

页数：9

共 37 条

[1] Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness [J].

Acland, GM ;

Aguirre, GD ;

Bennett, J ;

Aleman, TS ;

Cideciyan, AV ;

Bennicelli, J ;

Dejneka, NS ;

Pearce-Kelling, SE ;

Maguire, AM ;

Palczewski, K ;

Hauswirth, WW ;

Jacobson, SG .

MOLECULAR THERAPY, 2005, 12 (06) :1072-1082

[2] Gene therapy restores vision in a canine model of childhood blindness [J].

Acland, GM ;

Aguirre, GD ;

Ray, J ;

Zhang, Q ;

Aleman, TS ;

Cideciyan, AV ;

Pearce-Kelling, SE ;

Anand, V ;

Zeng, Y ;

Maguire, AM ;

Jacobson, SG ;

Hauswirth, WW ;

Bennett, J .

NATURE GENETICS, 2001, 28 (01) :92-95

[3]

Aguirre G D, 1998, Mol Vis, V4, P23

[4] A deviant immune response to viral proteins and transgene product is generated on subretinal administration of adenovirus and adeno-associated virus [J].

Anand, V ;

Duffy, B ;

Yang, ZX ;

Dejneka, NS ;

Maguire, AM ;

Bennett, J .

MOLECULAR THERAPY, 2002, 5 (02) :125-132

[5] Additional transduction events after subretinal readministration of recombinant adeno-associated virus [J].

Anand, V ;

Chirmule, N ;

Fersh, M ;

Maguire, AM ;

Bennett, J .

HUMAN GENE THERAPY, 2000, 11 (03) :449-457

[6] Effect of gene therapy on visual function in Leber's congenital amaurosis [J].

Bainbridge, James W. B. ;

Smith, Alexander J. ;

Barker, Susie S. ;

Robbie, Scott ;

Henderson, Robert ;

Balaggan, Kamaljit ;

Viswanathan, Ananth ;

Holder, Graham E. ;

Stockman, Andrew ;

Tyler, Nick ;

Petersen-Jones, Simon ;

Bhattacharya, Shomi S. ;

Thrasher, Adrian J. ;

Fitzke, Fred W. ;

Carter, Barrie J. ;

Rubin, Gary S. ;

Moore, Anthony T. ;

Ali, Robin R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (21) :2231-2239

[7] Subretinal delivery of adeno-associated virus serotype 2 results in minimal immune responses that allow repeat vector administration in immunocompetent mice [J].

Barker, Susie E. ;

Broderick, Cathryn A. ;

Robbie, Scott J. ;

Duran, Yanai ;

Natkunarajah, Mythili ;

Buch, Prateek ;

Balaggan, Kamaljit S. ;

MacLaren, Robert E. ;

Bainbridge, James W. B. ;

Smith, Alexander J. ;

Ali, Robin R. .

JOURNAL OF GENE MEDICINE, 2009, 11 (06) :486-497

[8] Reversal of blindness in animal models of Leber congenital amaurosis using optimized AAV2-mediated gene transfer [J].

Bennicelli, Jeannette ;

Wright, John Fraser ;

Komaromy, Andras ;

Jacobs, Jonathan B. ;

Hauck, Bernd ;

Zelenaia, Olga ;

Mingozzi, Federico ;

Hui, Daniel ;

Chung, Daniel ;

Rex, Tonia S. ;

Wei, Zhangyong ;

Qu, Guang ;

Zhou, Shangzhen ;

Zeiss, Caroline ;

Arruda, Valder R. ;

Acland, Gregory M. ;

Dell'Osso, Lou F. ;

High, Katherine A. ;

Maguire, Albert M. ;

Bennett, Jean .

MOLECULAR THERAPY, 2008, 16 (03) :458-465

[9] High-titer adeno-associated viral vectors from a Rep/Cap cell line and hybrid shuttle virus [J].

Gao, GP ;

Qu, G ;

Faust, LZ ;

Engdahl, RK ;

Xiao, WD ;

Hughes, JV ;

Zoltick, PW ;

Wilson, JM .

HUMAN GENE THERAPY, 1998, 9 (16) :2353-2362

[10] A novel method for objective vision testing in canine models of inherited retinal disease [J].

Gearhart, Patricia M. ;

Gearhart, Chris C. ;

Petersen-Jones, Simon M. .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2008, 49 (08) :3568-3576

← 1 2 3 4 →