Evaluating the transduction efficiency of systemically delivered AAV vectors in the rat nervous system.
Evaluating the transduction efficiency of systemically delivered AAV vectors in the rat nervous system.
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DOI：
10.3389/fnins.2023.1001007
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发表时间：
2023
影响因子：
4.3
通讯作者：
Mickle, Aaron D. D.
中科院分区：
文献类型：
--
作者：
Yang, Olivia J. J.;Robilotto, Gabriella L. L.;Alom, Firoj;Aleman, Karla;Devulapally, Karthik;Morris, Abigail;Mickle, Aaron D. D.
关键词：
基因传递或操纵与病毒载体是一种常用的工具，在基础神经科学研究。腺相关病毒（AAV）是最广泛使用的载体，由于其相对安全性和长期有效性，而不会引起明显的免疫并发症。已经发现并工程化了许多AAV血清型，其优先地覆盖不同的神经元群体。然而，外周神经元的有效靶向对于许多研究人员来说仍然具有挑战性，并且在大鼠中用AAV进行外周神经元转导的评估是有限的。在此，我们的目的是测试系统性AAV对大鼠外周神经元增殖的效率。我们通过腹膜内注射向新生大鼠全身施用AAV 9-tdTomato、AAV-PHP.S-tdTomato或AAV-retro-GFP。5周后，我们评估了外周感觉、运动和自主神经元的表达模式。在感觉神经元的转导中没有注意到血清型之间的显著差异，并且与较小的CGRP +神经元相比，所有血清型在转导NF 200+神经元中更有效。与其他血清型相比，AAV-逆转录在转导运动神经元方面更有效。此外，PHP.S在转导交感神经元方面更有效，而AAV-retro在转导副交感神经元方面更有效。这些结果表明，特定的AAV血清型靶向周围神经元群体更有效地比其他新生大鼠。
Gene delivery or manipulation with viral vectors is a frequently used tool in basic neuroscience studies. Adeno-associated viruses (AAV) are the most widely used vectors due to their relative safety and long-term efficacy without causing overt immunological complications. Many AAV serotypes have been discovered and engineered that preferentially transduce different populations of neurons. However, efficient targeting of peripheral neurons remains challenging for many researchers, and evaluation of peripheral neuron transduction with AAVs in rats is limited. Here, we aimed to test the efficiency of systemic AAVs to transduce peripheral neurons in rats. We administered AAV9-tdTomato, AAV-PHP.S-tdTomato, or AAV-retro-GFP systemically to neonatal rats via intraperitoneal injection. After 5 weeks, we evaluated expression patterns in peripheral sensory, motor, and autonomic neurons. No significant difference between the serotypes in the transduction of sensory neurons was noted, and all serotypes were more efficient in transducing NF200 + neurons compared to smaller CGRP + neurons. AAV-retro was more efficient at transducing motor neurons compared to other serotypes. Moreover, PHP.S was more efficient at transducing sympathetic neurons, and AAV-retro was more efficient at transducing parasympathetic neurons. These results indicate that specific AAV serotypes target peripheral neuron populations more efficiently than others in the neonatal rat.
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影响因子：
16.2
作者：
Chen, Xinhong;Kumar, Sripriya Ravindra;Adams, Cameron D.;Yang, Daping;Wang, Tongtong;Wolfe, Damien A.;Arokiaraj, Cynthia M.;Ngo, Victoria;Campos, Lillian J.;Griffiths, Jessica A.;Ichiki, Takako;Mazmanian, Sarkis K.;Osborne, Peregrine B.;Keast, Janet R.;Miller, Cory T.;Fox, Andrew S.;Chiu, Isaac M.;Gradinaru, Viviana
通讯作者：
Gradinaru, Viviana
影响因子：
25
作者：
Chan KY;Jang MJ;Yoo BB;Greenbaum A;Ravi N;Wu WL;Sánchez-Guardado L;Lois C;Mazmanian SK;Deverman BE;Gradinaru V
通讯作者：
Gradinaru V
影响因子：
4.7
作者：
Jackson, Kasey L.;Dayton, Robert D.;Klein, Ronald L.
通讯作者：
Klein, Ronald L.
影响因子：
3.3
作者：
Yu H;Fischer G;Jia G;Reiser J;Park F;Hogan QH
通讯作者：
Hogan QH
影响因子：
4.2
作者：
Gray, Steven J.;Foti, Stacey B.;Samulski, R. Jude
通讯作者：
Samulski, R. Jude