腺相关病毒的基因疗法在心血管疾病中的应用

Adeno-associated virus-based gene therapy for cardiovascular diseases

尽管现代医疗手段不断改进,但心血管疾病(cardiovascular diseases,CVD)的病死率仍居高不下,寻找新的防治方法将具有良好的临床应用前景。腺相关病毒(adeno-associated virus,AAV)作为基因治疗的载体之一,可以通过基因替代、基因沉默、递送新基因、基因编辑等方式在CVD中起到治疗作用。AAV有多种血清型,其中AAV1型、6型、8型、9型对心脏有组织亲和性,并且转导后能在体内稳定长效表达,安全性高。该文主要针对AAV基因疗法在心力衰竭、冠心病、肥厚型心肌病、扩张型心肌病以及心律失常等CVD中的应用进行综述。目前,AAV载体在克服宿主中和抗体、心脏选择性以及注射剂量和途径的优化等方面仍存在一些挑战,利用外泌体包裹AAV以克服宿主抗体中和,基于CRISPR/Cas9基因编辑技术设计有心脏或血管特异性启动子的AAV载体等改进方法还需要进一步探索。因此,AAV基因治疗在心血管领域还有很大的研发空间和很好的应用价值。

Despite the improvement of modern medical methods,the mortality rate of cardiovascular diseases(CVD)is still high.Finding new prevention and treatment methods will have good clinical application prospects.Adeno-associated virus(AAV),one of the vectors for gene therapy,can play a therapeutic role in CVD through gene replacement,gene silencing,gene addition,and gene editing.There are many serotypes of AAV,among which AAV1,6,8 and 9 have cardiac tropism.AAVs can be expressed stably and for long-term in the body with high safety.This article mainly reviewed the application of AAV gene therapy in CVD such as heart failure,coronary heart disease,hypertrophic cardiomyopathy,dilated cardiomyopathy and arrhythmia.At present,there are still some challenges for AAV vector in overcoming the neutralizing antibody of host,cardiac selectivity,and optimization of injection dose and route.Further exploration is needed in using exosome to encapsulate AAV to overcome neutralization of host antibody,and designing AAV vector with cardiac-or vascular-specific promoter based on CRISPR/Cas9 gene editing technology.Therefore,AAV gene therapy in the cardiovascular field still needs a lot of researches and has a good application value.