Dosage thresholds for AAV2 and AAV8 photoreceptor gene therapy in monkey.
Dosage thresholds for AAV2 and AAV8 photoreceptor gene therapy in monkey.
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DOI：
10.1126/scitranslmed.3002103
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发表时间：
2011-06-22
影响因子：
17.1
通讯作者：
Bennett J
中科院分区：
文献类型：
--
作者：
Vandenberghe LH;Bell P;Maguire AM;Cearley CN;Xiao R;Calcedo R;Wang L;Castle MJ;Maguire AC;Grant R;Wolfe JH;Wilson JM;Bennett J
Gene therapy is emerging as a therapeutic modality for treating disorders of the retina. Photoreceptor cells are the primary cell type affected in many inherited diseases of retinal degeneration. Successfully treating these diseases with gene therapy requires the identification of efficient and safe targeting vectors that can transduce photoreceptor cells. One serotype of adeno-associated virus, AAV2, has been used successfully in clinical trials to treat a form of congenital blindness that requires transduction of the supporting cells of the retina in the retinal pigment epithelium (RPE). Here, we determined the dose required to achieve targeting of AAV2 and AAV8 vectors to photoreceptors in nonhuman primates. Transgene expression in animals injected subretinally with various doses of AAV2 or AAV8 vectors carrying a green fluorescent protein transgene was correlated with surgical, clinical, and immunological observations. Both AAV2 and AAV8 demonstrated efficient transduction of RPE, but AAV8 was markedly better at targeting photoreceptor cells. These preclinical results provide guidance for optimal vector and dose selection in future human gene therapy trials to treat retinal diseases caused by loss of photoreceptors.
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影响因子：
4.2
作者：
GLATT, H;MACHEMER, R
通讯作者：
MACHEMER, R
成人灵长类动物红绿色色盲的基因疗法。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
17.8
作者：
Berger, Wolfgang;Kloeckener-Gruissem, Barbara;Neidhardt, John
通讯作者：
Neidhardt, John
影响因子：
5.1
作者：
Bainbridge, JWB;Mistry, A;Ali, RR
通讯作者：
Ali, RR
影响因子：
4.2
作者：
Hauswirth, William W.;Aleman, Tomas S.;Jacobson, Samuel G.
通讯作者：
Jacobson, Samuel G.