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Delivery of deoxyribonucleic acid (DNA) to somatic cells: An overview of species and strain-related responses [Review]

机译:脱氧核糖核酸(DNA)传递到体细胞:物种和菌株相关反应的概述[综述]

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摘要

There is great potential in successful delivery of genetic material to somatic cells of animals and humans, not only to treat genetic deficiencies, but also to provide more effective therapies and vaccines. Concerted effort has been mounted over the past decade to validate the concept of gene-based therapy. Delivery of genes in vitro via multiple methods has demonstrated the biologic usefulness of the basic concept. However, application of similar gene delivery strategies to whole animal systems has been more difficult. Much of the complexity associated with gene delivery involves encounters with host biological barriers, including innate and acquired host responses to exogenous DNA, as well as specifically encoded proteins. Delivery of genetic material to somatic cells in vivo is a multi-factorial event involving variables in formulation, route, and dose, and target species or strain. In vivo expression of these variables can result in conflicting findings with regard to gene expression and toxicity. These findings may compromise the predictive reliability of interstrain and, particularly, interspecies studies. This review will address representative in vivo somatic cell transfection modalities, variability in species and strain responses following delivery of nucleic acids, and some of the potential mechanisms involved.
机译:成功地将遗传物质传递给动物和人类体细胞的巨大潜力,不仅可以治疗遗传缺陷,而且可以提供更有效的疗法和疫苗。在过去的十年中,人们齐心协力来验证基于基因的疗法的概念。通过多种方法体外传递基因已证明了基本概念的生物学用途。然而,将相似的基因递送策略应用于整个动物系统却更加困难。与基因传递相关的许多复杂性涉及宿主生物屏障的遭遇,包括对外源DNA以及特异编码蛋白质的先天和后天宿主应答。遗传物质在体内向体细胞的传递是一个多因素事件,涉及制剂,途径和剂量以及目标物种或菌株的变量。这些变量的体内表达可能导致有关基因表达和毒性的发现相互矛盾。这些发现可能会损害跨株,尤其是种间研究的预测可靠性。这项审查将解决代表性的体内体细胞转染方式,核酸交付后物种和菌株反应的变异性,以及涉及的一些潜在机制。

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