Current strategies for myocardial gene delivery.
Current strategies for myocardial gene delivery.
复制标题
DOI：
10.1016/j.yjmcc.2010.09.003
复制
发表时间：
2011-05
影响因子：
5
通讯作者：
Bridges CR
中科院分区：
文献类型：
--
作者：
Katz MG;Swain JD;Tomasulo CE;Sumaroka M;Fargnoli A;Bridges CR
现有的心脏基因递送方法可以根据注射部位、介入方法和转移时的心脏循环类型进行分类。评估给定递送方法功效的一般标准包括：全局与区域心肌转导、技术复杂性和与其使用相关的病理生理学效应、递送相关的侧支表达以及递送相关的炎症和免疫反应。直接基因递送（心肌内、心内膜、心外膜）可用于治疗性血管生成和局灶性心律失常治疗，但基因表达主要限于靠近注射部位的区域。这些技术的一个经常被忽视的局限性是它们经常与大量的全身载体传递相关。经皮将载体输注到冠状动脉中是微创的，并且允许将转基因递送到整个心肌。不幸的是，冠状动脉内递送的效率变化很大，并且载体在冠状循环内的短暂停留时间和显着的侧支器官表达限制了其临床潜力。外科技术，包括将体外循环与孤立的心脏再循环相结合，代表了可能克服这些局限性的新颖的输送策略；然而，这些技术很复杂，具有固有的发病率，在安全转化为临床实践之前必须对其进行彻底评估。基因递送最佳技术的特点包括低发病率、增加的心肌跨毛细血管梯度、延长载体在冠状循环中的停留时间以及递送后从体循环中排除残余载体以最小化心外表达并减轻细胞免疫反应。本文是题为“特别章节：心血管基因治疗”的特别章节的一部分。
Existing methods of cardiac gene delivery can be classified by the site of injection, interventional approach and type of cardiac circulation at the time of transfer. General criteria to assess the efficacy of a given delivery method include: global versus regional myocardial transduction, technical complexity and the pathophysiological effects associated with its use, delivery-related collateral expression and the delivery-associated inflammatory and immune response. Direct gene delivery (intramyocardial, endocardial, epicardial) may be useful for therapeutic angiogenesis and for focal arrhythmia therapy but with gene expression which is primarily limited to regions in close proximity to the injection site. An often unappreciated limitation of these techniques is that they are frequently associated with substantial systemic vector delivery. Percutaneous infusion of vector into the coronary arteries is minimally invasive and allows for transgene delivery to the whole myocardium. Unfortunately, efficiency of intracoronary delivery is highly variable and the short residence time of vector within the coronary circulation and significant collateral organ expression limit its clinical potential. Surgical techniques, including the incorporation of cardiopulmonary bypass with isolated cardiac recirculation, represent novel delivery strategies that may potentially overcome these limitations; yet, these techniques are complex with inherent morbidity that must be thoroughly evaluated before safe translation into clinical practice. Characteristics of the optimal technique for gene delivery include low morbidity, increased myocardial transcapillary gradient, extended vector residence time in the coronary circulation and exclusion of residual vector from the systemic circulation after delivery to minimize extracardiac expression and to mitigate a cellular immune response. This article is part of a Special Section entitled “Special Section: Cardiovascular Gene Therapy”.
登录
查看更多内容
DOI：
10.1073/pnas.95.9.5251
发表时间：
1998-04-28
影响因子：
11.1
作者：
Hajjar, RJ;Schmidt, U;Rosenzweig, A
通讯作者：
Rosenzweig, A
影响因子：
1.6
作者：
Baker, AH
通讯作者：
Baker, AH
DOI：
10.1016/s1043-0679(03)70006-9
发表时间：
2003-07-01
影响因子：
2.5
作者：
Bernecker, Oliver Y;del Monte, Federica;Hajjar, Roger J
通讯作者：
Hajjar, Roger J
DOI：
10.1196/annals.1302.029
发表时间：
2004-01-01
期刊：
CARDIAC ENGINEERING: FROM GENES AND CELLS TO STRUCTURE AND FUNCTION
影响因子：
--
作者：
Donahue, JK
通讯作者：
Donahue, JK
影响因子：
5.1
作者：
Byrne, M. J.;Power, J. M.;Kaye, D. M.
通讯作者：
Kaye, D. M.