High cerebrospinal fluid levels of interleukin-10 attained by AAV in dogs.
High cerebrospinal fluid levels of interleukin-10 attained by AAV in dogs.
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AAV在狗中获得的白细胞介素10的高脑脊液水平。
DOI：
10.1038/gt.2014.96
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发表时间：
2015-02
期刊：
影响因子：
5.1
通讯作者：
Beutler, A. S.
中科院分区：
文献类型：
--
作者：
Pleticha, J.;Malkmus, S. A.;Heilmann, L. F.;Veesart, S. L.;Rezek, R.;Xu, Q.;Yaksh, T. L.;Beutler, A. S.
Intrathecal (IT) gene transfer using adeno-associated virus (AAV) may be clinically promising as a treatment for chronic pain if it can produce sufficiently high levels of a transgene product in the cerebrospinal fluid (CSF). While this strategy was developed in rodents, no studies investigating CSF levels of an analgesic or anti-allodynic protein delivered by IT AAV have been performed in large animals. Interleukin-10 (IL-10) is an anti-allodynic cytokine, for which target therapeutic levels have been established in rats. The present study tested IT AAV8 encoding either human IL-10 (hIL-10) or enhanced green fluorescent protein (EGFP) in a dog model of IT drug delivery. AAV8/hIL-10 at a dose of 3.5×1012 genome copies induced high hIL-10 levels in the CSF, exceeding the target concentration previously found to be anti-allodynic in rodents by >1000-fold. AAV8/EGFP targeted the primary sensory and motor neurons and the meninges. hIL-10, a xenogeneic protein in dogs, induced anti-hIL-10 antibodies detectable in the dogs’ CSF and serum. The high hIL-10 levels demonstrate the efficacy of AAV for delivery of secreted transgenes into the IT space of large animals suggesting a strong case for further development towards clinical testing.
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单纯疱疹病毒介导的白细胞介素-10的表达减少了脊髓损伤后的中枢性神经性疼痛。
影响因子：
4.2
作者：
Lau D;Harte SE;Morrow TJ;Wang S;Mata M;Fink DJ
通讯作者：
Fink DJ
内部对流增强了靶向主要感觉神经元的AAVRH20的递送。
DOI：
10.1016/j.mcn.2014.04.004
发表时间：
2014-05
期刊：
Molecular and cellular neurosciences
影响因子：
--
作者：
Pleticha J;Jeng-Singh C;Rezek R;Zaibak M;Beutler AS
通讯作者：
Beutler AS
DOI：
10.1111/j.1525-1403.2012.00462.x
发表时间：
2012-11
期刊：
Neuromodulation : journal of the International Neuromodulation Society
影响因子：
--
作者：
Milligan ED;Penzkover KR;Soderquist RG;Mahoney MJ
通讯作者：
Mahoney MJ
影响因子：
4.8
作者：
Chen, GJ;Castro, WL;Reichlin, S
通讯作者：
Reichlin, S
影响因子：
11.2
作者：
Ciron, Carine;Desmaris, Nathalie;Heard, Jean-Michel
通讯作者：
Heard, Jean-Michel