Cardiac gene therapy with adeno-associated virus-based vectors.
Cardiac gene therapy with adeno-associated virus-based vectors.
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DOI：
10.1097/hco.0000000000000386
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发表时间：
2017-05
影响因子：
2.3
通讯作者：
Weber T
中科院分区：
文献类型：
--
作者：
Chamberlain K;Riyad JM;Weber T
用腺相关病毒(AAV)为载体的心脏基因治疗正在成为治疗甚至治愈迄今难治性心脏疾病的全新平台。本文介绍了我们目前对心脏AAV基因治疗的认识，重点介绍了心脏AAV基因治疗成功应用于临床的最大障碍，即有效地将治疗性基因输送到心肌。我们总结了在临床前相关动物模型中使用AAV基因治疗心力衰竭方面取得的重要进展，以及心脏AAV基因治疗心力衰竭的临床试验的最新结果。我们还讨论了目前可用的AAV心脏递送方法的优点和缺点。最后，我们描述了识别新的AAV变异体的现状，这些变异体增强了对人类心肌细胞的趋向性，并对先前存在的中和抗体表现出更强的抵抗力。在这里，我们描述了心脏AAV基因治疗的成功和挑战，这种治疗方式有可能改变目前心脏疾病的治疗方法。
Cardiac gene therapy with adeno-associated virus (AAV)-based vectors is emerging as an entirely new platform to treat, or even cure, so far intractable cardiac disorders. This review describes our current knowledge of cardiac AAV gene therapy with a particular focus on the biggest obstacle for the successful translation of cardiac AAV gene therapy into the clinic, namely the efficient delivery of the therapeutic gene to the myocardium. We summarize the significant recent progress that has been made in treating heart failure in preclinically relevant animal models with AAV gene therapy and the recent results of clinical trials with cardiac AAV gene therapy for the treatment of heart failure. We also discuss the benefits and shortcomings of the currently available delivery methods of AAV to the heart. Finally, we describe the current state of identifying novel AAV variants that have enhanced tropism for human cardiomyocytes and that show increased resistance to pre-existing neutralizing antibodies. Here we describe the successes and challenges in cardiac AAV gene therapy, a treatment modality that has the potential to transform current treatment approaches for cardiac diseases.