Systemic gene delivery transduces the enteric nervous system of guinea pigs and cynomolgus macaques.
Systemic gene delivery transduces the enteric nervous system of guinea pigs and cynomolgus macaques.
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DOI：
10.1038/gt.2017.72
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发表时间：
2017-10
期刊：
影响因子：
5.1
通讯作者：
Foust KD
中科院分区：
文献类型：
--
作者：
Gombash SE;Cowley CJ;Fitzgerald JA;Lepak CA;Neides MG;Hook K;Todd LJ;Wang GD;Mueller C;Kaspar BK;Bielefeld EC;Fischer AJ;Wood JD;Foust KD
腺相关病毒载体（AAV）介导的基因递送到肠神经系统（ENS）的表征最近在小鼠和大鼠中被描述。在这些概念验证实验中，我们表明，静脉注射临床相关的AAV可以使豚鼠和非人灵长类动物的ENS萎缩。对新生豚鼠静脉内注射含有绿色荧光蛋白（GFP）表达盒的AAV 8或AAV 9载体或PBS。注射后三周对仔猪实施安乐死，收获组织用于免疫荧光分析。在注射AAV 8的豚鼠中，沿着胃肠道的长度在肌间和粘膜下神经元沿着中检测到GFP表达。在迷走神经运动背核和背根神经节内可见GFP阳性神经元。在AAV9处理的组织中发生较少的转导。分析来自接受全身注射AAV9 GFP的年轻食蟹猴的胃肠道组织。在胃、小肠和大肠的肌间神经元中检测到GFP表达。这些数据表明ENS基因递送转化为更大的物种。这项工作为神经胃肠病学领域开发了工具，利用光遗传学和基因编辑等新兴技术探索肠道生理学和解剖学。它还为开发慢性肠道疾病的新疗法提供了基础。
Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or PBS. Piglets were euthanized three weeks post-injection and tissues were harvested for immunofluorescent analysis. GFP expression was detected in myenteric and submucosal neurons along the length of the gastrointestinal tract in AAV8 injected guinea pigs. GFP positive neurons were found in dorsal motor nucleus of the vagus and dorsal root ganglia. Less transduction occurred in AAV9 treated tissues. Gastrointestinal tissues were analyzed from young cynomolgus macaques that received systemic injection of AAV9 GFP. GFP expression was detected in myenteric neurons of the stomach, small and large intestine. These data demonstrate that ENS gene delivery translates to larger species. This work develops tools for the field of neurogastroenterology to explore gut physiology and anatomy using emerging technologies such as optogenetics and gene editing. It also provides a basis to develop novel therapies for chronic gut disorders.
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影响因子：
12.4
作者：
Duque, Sandra;Joussemet, Beatrice;Barkats, Martine
通讯作者：
Barkats, Martine
影响因子：
5.4
作者：
Akache, Bassel;Grimm, Dirk;Kay, Mark A.
通讯作者：
Kay, Mark A.
影响因子：
5.5
作者：
Buckley, Maria M.;O'Halloran, Ken D.;O'Malley, Dervla
通讯作者：
O'Malley, Dervla
用于针对小儿疾病的脊髓，大脑和周围组织的大物种中的全身基因递送。
DOI：
10.1038/mt.2011.157
发表时间：
2011-11
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.5
作者：
Bergner, Annette J.;Stamp, Lincon A.;Gonsalvez, David G.;Allison, Margaret B.;Olson, David P.;Myers, Martin G., Jr.;Anderson, Colin R.;Young, Heather M.
通讯作者：
Young, Heather M.