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腺相关病毒血清型 rh.10 经腹腔给药后显示出强烈的肌肉趋向性。

Adeno-associated virus serotype rh.10 displays strong muscle tropism following intraperitoneal delivery.

机构信息

Institute of Urology, Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China.

Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

出版信息

Sci Rep. 2017 Jan 9;7:40336. doi: 10.1038/srep40336.

Abstract

Recombinant adeno-associated virus (rAAV) is an attractive tool for basic science and translational medicine including gene therapy, due to the versatility in its cell and organ transduction. Previous work indicates that rAAV transduction patterns are highly dependent on route of administration. Based on this relationship, we hypothesized that intraperitoneal (IP) administration of rAAV produces unique patterns of tissue tropism. To test this hypothesis, we investigated the transduction efficiency of 12 rAAV serotypes carrying an enhanced green fluorescent protein (EGFP) reporter gene in a panel of 12 organs after IP injection. Our data suggest that IP administration emphasizes transduction patterns that are different from previously reported intravascular delivery methods. Using this approach, rAAV efficiently transduces the liver, pancreas, skeletal muscle, heart and diaphragm without causing significant histopathological changes. Of note, rAAVrh.10 showed excellent muscle transduction following IP administration, highlighting its potential as a new muscle-targeting vector.

摘要

重组腺相关病毒(rAAV)是基础科学和转化医学(包括基因治疗)的一种有吸引力的工具,因为它在细胞和器官转导方面具有多功能性。以前的工作表明,rAAV 的转导模式高度依赖于给药途径。基于这种关系,我们假设腹腔内(IP)给予 rAAV 会产生独特的组织嗜性模式。为了验证这一假设,我们研究了携带增强型绿色荧光蛋白(EGFP)报告基因的 12 种 rAAV 血清型在 IP 注射后 12 种器官中的转导效率。我们的数据表明,IP 给药强调了与以前报道的血管内给药方法不同的转导模式。使用这种方法,rAAV 可以有效地转导肝脏、胰腺、骨骼肌、心脏和膈肌,而不会引起明显的组织病理学变化。值得注意的是,rAAVrh.10 在 IP 给药后表现出优异的肌肉转导,突出了其作为新型肌肉靶向载体的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa05/5220346/521fc398541b/srep40336-f1.jpg

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