Persistent expression of FLAG-tagged micro dystrophin in nonhuman primates following intramuscular and vascular delivery.
Persistent expression of FLAG-tagged micro dystrophin in nonhuman primates following intramuscular and vascular delivery.
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DOI：
10.1038/mt.2009.254
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发表时间：
2010-01
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--
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Animal models for Duchenne muscular dystrophy (DMD) have species limitations related to assessing function, immune response, and distribution of micro- or mini-dystrophins. Nonhuman primates (NHPs) provide the ideal model to optimize vector delivery across a vascular barrier and provide accurate dose estimates for widespread transduction. To address vascular delivery and dosing in rhesus macaques, we have generated a fusion construct that encodes an eight amino-acid FLAG epitope at the C-terminus of micro-dystrophin to facilitate translational studies targeting DMD. Intramuscular (IM) injection of AAV8.MCK.micro-dys.FLAG in the tibialis anterior (TA) of macaques demonstrated robust gene expression, with muscle transduction (50–79%) persisting for up to 5 months. Success by IM injection was followed by targeted vascular delivery studies using a fluoroscopy-guided catheter threaded through the femoral artery. Three months after gene transfer, >80% of muscle fibers showed gene expression in the targeted muscle. No cellular immune response to AAV8 capsid, micro-dystrophin, or the FLAG tag was detected by interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) at any time point with either route. In summary, an epitope-tagged micro-dystrophin cassette enhances the ability to evaluate site-specific localization and distribution of gene expression in the NHP in preparation for vascular delivery clinical trials.
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影响因子：
7.4
作者：
Rodino-Klapac, Louise R.;Janssen, Paul M. L.;Mendell, Jerry R.
通讯作者：
Mendell, Jerry R.
影响因子：
12.4
作者：
Townsend, DeWayne;Blankinship, Michael J.;Metzger, Joseph M.
通讯作者：
Metzger, Joseph M.
DOI：
10.1073/pnas.93.24.14082
发表时间：
1996-11-26
影响因子：
11.1
作者：
Kessler, PD;Podsakoff, GM;Byrne, BJ
通讯作者：
Byrne, BJ
DOI：
10.1038/nbt1088-1204
发表时间：
1988-10-01
期刊：
BIO-TECHNOLOGY
影响因子：
--
作者：
HOPP, TP;PRICKETT, KS;CONLON, PJ
通讯作者：
CONLON, PJ
在肌动蛋白结合结构域中表达肌营养不良蛋白的转基因MDX小鼠表现出“轻度贝克”表型。
影响因子：
7.8
作者：
Corrado, K;Rafael, JA;Mills, PL;Cole, NM;Faulkner, JA;Wang, K;Chamberlain, JS
通讯作者：
Chamberlain, JS