Adeno-associated virus-vectored gene therapy for retinal disease

被引:79
作者
Dinculescu, A
Glushakova, L
Min, SH
Hauswirth, WW
机构
[1] Univ Florida, Coll Med, Dept Ophthalmol, J Hillis Miller Hlth Ctr, Gainesville, FL 32610 USA
[2] Univ Florida, Powell Gene Therapy Ctr, Gainesville, FL 32610 USA
关键词
D O I
10.1089/hum.2005.16.649
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 (AAV) vectors have become powerful gene delivery tools for the treatment of retinal degeneration in a variety of animal models that mimic corresponding human diseases. AAV vectors possess a number of features that render them ideally suited for retinal gene therapy, including a lack of pathogenicity, minimal immunogenicity, and the ability to transduce postmitotic cells in a stable and efficient manner. In the sheltered environment of the retina, AAV vectors are able to maintain high levels of transgene expression in the retinal pigmented epithelium ( RPE), photoreceptors, or ganglion cells for long periods of time after a single treatment. Each cell type can be specifically targeted by choosing the appropriate combination of AAV serotype, promoter, and intraocular injection site. The focus of this review is on examples of AAV-mediated gene therapy in those animal models of inherited retinal degeneration caused by mutations directly affecting the interacting unit formed by photoreceptors and the RPE. In each case discussed, expression of the therapeutic gene resulted in significant recovery of retinal structure and/or visual function. Because of the key role of the vasculature in maintaining a healthy retina, a summary of AAV gene therapy applications in animal models of retinal neovascular diseases is also included.
引用
收藏
页码:649 / 663
页数:15
相关论文
共 174 条
[91]   Adeno-associated virus type 5: Transduction efficiency and cell-type specificity in the primate retina [J].
Lotery, AJ ;
Yang, GS ;
Mullins, RF ;
Russell, SR ;
Schmidt, M ;
Stone, EM ;
Lindbloom, JD ;
Chiorini, JA ;
Kotin, RM ;
Davidson, BL .
HUMAN GENE THERAPY, 2003, 14 (17) :1663-1671
[92]   Recombinant adeno-associated virus as delivery vector for gene therapy - A review [J].
Lu, Y .
STEM CELLS AND DEVELOPMENT, 2004, 13 (01) :133-145
[93]   Retinal and optic nerve diseases [J].
Margalit, E ;
Sadda, TR .
ARTIFICIAL ORGANS, 2003, 27 (11) :963-974
[94]   Mutations in RPE65 cause Leber's congenital amaurosis [J].
Marlhens, F ;
Bareil, C ;
Griffoin, JM ;
Zrenner, E ;
Amalric, P ;
Eliaou, C ;
Liu, SY ;
Harris, E ;
Redmond, TM ;
Arnaud, B ;
Claustres, M ;
Hamel, CP .
NATURE GENETICS, 1997, 17 (02) :139-141
[95]   Gene delivery to the eye using adeno-associated viral vectors [J].
Martin, KRG ;
Klein, RL ;
Quigley, HA .
METHODS, 2002, 28 (02) :267-275
[96]   Rpe65 is a retinyl ester binding protein that presents insoluble substrate to the isomerase in retinal pigment epithelial cells [J].
Mata, NL ;
Moghrabi, WN ;
Lee, JS ;
Bui, TV ;
Radu, RA ;
Horwitz, J ;
Travis, GH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (01) :635-643
[97]  
Mieziewska K, 1996, MICROSC RES TECHNIQ, V35, P463
[98]  
MILLER H, 1990, INVEST OPHTH VIS SCI, V31, P899
[99]  
MIN SH, 2005, UNPUB PROLONGED RECO
[100]   Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse [J].
Mohand-Said, S ;
Deudon-Combe, A ;
Hicks, D ;
Simonutti, M ;
Forster, V ;
Fintz, AC ;
Leveillard, T ;
Dreyfus, H ;
Sahel, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (14) :8357-8362