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一种基于增强子的基因治疗策略在组织修复过程中对货物进行时空控制
2022-12-15 15:41
来源：小柯机器人

美国杜克大学医学院Kenneth D. Poss小组提出了一种基于增强子的基因治疗策略，可用于组织修复期间对货物的时空控制。这一研究成果于2022年12月13日在线发表在国际学术期刊《细胞—干细胞》上。

研究人员发现，从斑马鱼中分离出来的组织再生增强子元件（TREE）可以引导来自病毒DNA载体的有针对性的、与损伤相关的基因表达，并在小型和大型成年哺乳动物物种中进行系统传递。当在小鼠中与基于CRISPR的表观基因组编辑工具结合使用时，斑马鱼的TREE在缺血性心肌梗塞后刺激或抑制内源性基因的表达。静脉递送的重组AAV载体设计了一个TREE来引导组成性活化的YAP因子，从而促进了小鼠心脏再生的指标，并改善了受伤心脏的功能。这些研究结果表明，背景依赖的增强子元件的应用是一个潜在的治疗平台，可用于哺乳动物的时空控制组织再生。
 
据介绍，针对组织损伤等适应症的基因治疗策略的有效性和安全性取决于精确性。然而，目前的方法对有效载荷的输送几乎没有空间或时间控制。
 
附：英文原文

Title: An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair

Author: Ruorong Yan, Valentina Cigliola, Kelsey A. Oonk, Zachary Petrover, Sophia DeLuca, David W. Wolfson, Andrew Vekstein, Michelle A. Mendiola, Garth Devlin, Muath Bishawi, Matthew P. Gemberling, Tanvi Sinha, Michelle A. Sargent, Allen J. York, Avraham Shakked, Paige DeBenedittis, David C. Wendell, Jianhong Ou, Junsu Kang, Joseph A. Goldman, Gurpreet S. Baht, Ravi Karra, Adam R. Williams, Dawn E. Bowles, Aravind Asokan, Eldad Tzahor, Charles A. Gersbach, Jeffery D. Molkentin, Nenad Bursac, Brian L. Black, Kenneth D. Poss

Issue&Volume: 2022-12-13

Abstract: The efficacy and safety of gene-therapy strategies for indications like tissue damagehinge on precision; yet, current methods afford little spatial or temporal controlof payload delivery. Here, we find that tissue-regeneration enhancer elements (TREEs)isolated from zebrafish can direct targeted, injury-associated gene expression fromviral DNA vectors delivered systemically in small and large adult mammalian species.When employed in combination with CRISPR-based epigenome editing tools in mice, zebrafishTREEs stimulated or repressed the expression of endogenous genes after ischemic myocardialinfarction. Intravenously delivered recombinant AAV vectors designed with a TREE todirect a constitutively active YAP factor boosted indicators of cardiac regenerationin mice and improved the function of the injured heart. Our findings establish theapplication of contextual enhancer elements as a potential therapeutic platform forspatiotemporally controlled tissue regeneration in mammals.

DOI: 10.1016/j.stem.2022.11.012

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00459-3

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
官方网址：https://www.cell.com/cell-stem-cell/home
投稿链接：https://www.editorialmanager.com/cell-stem-cell/default.aspx


本期文章：《细胞—干细胞》：Online/在线发表

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