摘要
尽管重组腺相关病毒(rAAV)基因治疗对Duchenne型肌营养不良症(DMD)动物模型有着前所未有的有益效果,而需要在体内注入大量的载体来改善表型却明显地增加了生物安全问题。而重组腺相关病毒载体通常表现出良好的安全性,在营养缺乏的肌肉里观察到的特定的病理表型,可能促进了免疫毒性/遗传毒性效应。通过降低有效剂量增加DMD肌肉的rAAV的治疗指数可能是保证有效的临床应用的关键手段。这需要全面的了解总是在非病变组织或体外被研究的重组腺相关病毒转导的过程。在这篇综述中,我们专注于注射后rAAV的分子命运,以及在DMD的情况下如何影响到转导的各个阶段。
关键词: 肌肉,杜氏肌肉营养不良症,腺相关病毒,基因治疗,制约因素,在体内。
Current Gene Therapy
Title:Restriction Factors Against Recombinant Adeno-associated Virus Vectormediated Gene Transfer in Dystrophin-deficient Muscles
Volume: 16 Issue: 3
Author(s): Jean-Baptiste Dupont
Affiliation:
关键词: 肌肉,杜氏肌肉营养不良症,腺相关病毒,基因治疗,制约因素,在体内。
摘要: Despite the unprecedented beneficial effects of rAAV gene therapy in animal models of Duchenne muscular dystrophy (DMD), the need to inject large amounts of vector in vivo to improve phenotype raises obvious biosafety concerns. While rAAV vectors generally exhibit a good safety profile, specific pathological phenotypes such as those observed in dystrophin-deficient muscles may promote immunotoxic/genotoxic effects. Increasing the therapeutic index of rAAV in DMD muscles by reducing the effective dose could be a pivotal means of ensuring efficient clinical translation. This requires a comprehensive understanding of the rAAV transduction process, which is almost always studied in non-pathological tissues or in vitro. In this review, we focus on the molecular fate of rAAV after injection, and how the individual stages of transduction could be affected in the context of DMD.
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Jean-Baptiste Dupont , Restriction Factors Against Recombinant Adeno-associated Virus Vectormediated Gene Transfer in Dystrophin-deficient Muscles, Current Gene Therapy 2016; 16 (3) . https://dx.doi.org/10.2174/1566523216666160428104325
DOI https://dx.doi.org/10.2174/1566523216666160428104325 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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