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大动物模型中的心脏基因递送:选择性逆行静脉注射。

Cardiac Gene Delivery in Large Animal Models: Selective Retrograde Venous Injection.

机构信息

Department of Internal Medicine III, Cardiology, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany.

DZHK [German Centre for Cardiovascular Research], Partner Site, Heidelberg/Mannheim, Germany.

出版信息

Methods Mol Biol. 2022;2573:171-177. doi: 10.1007/978-1-0716-2707-5_13.

Abstract

Delivery of viral vectors to the heart represents a challenging endeavor. Besides vector design, the route of substrate administration is significantly influencing gene delivery success. The selective retrograde venous injection (SRVI) represents one of the most efficient percutaneous delivery strategies for transduction of the anterior left ventricular myocardium. In this chapter, we discuss the advantages and limitations of this vector delivery approach and provide a protocol for selective retrograde venous injection in a preclinical large animal model. As limited transgene expression frequently hampers generation of reliable proof-of-principle data and thus translation, this technique provides a valuable tool to ensure high myocardial transduction in preclinical research.

摘要

将病毒载体递送到心脏是一项具有挑战性的工作。除了载体设计外,基底物给药途径对基因传递的成功有重要影响。选择性逆行静脉注射(SRVI)是一种最有效的经皮递药策略,可用于转导左心室前壁心肌。在本章中,我们讨论了这种载体传递方法的优缺点,并提供了在临床前大型动物模型中进行选择性逆行静脉注射的方案。由于有限的转基因表达经常阻碍可靠的原理验证数据的产生,因此该技术为确保临床前研究中的高心肌转导提供了有价值的工具。

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