神经肌肉疾病基因治疗的研究进展

Advances in gene therapy of neuromuscular diseases

神经肌肉疾病(neuromuscular diseases,NMD)是一类以运动单位受损、运动耐力下降、肌力减退为主要表现的中枢及周围神经疾病。长期以来,神经肌肉疾病的治疗手段主要是对症治疗,但仅能缓解症状,无法根治。腺相关病毒(adeno-associated virus,AAV)载体是经过基因工程改造过的转基因载体,由于其安全性好、免疫原性低、表达时间长,可以感染分裂细胞和非分裂细胞等特点,在基因治疗和疫苗研究中得到广泛应用。CRISPR/Cas9基因编辑系统由型CRISPR细菌免疫系统改进而来,具有靶向精确、脱靶率低、细胞毒性低等特点,是目前应用最为广泛的基因编辑工具。本综述总结了几种常见神经肌肉疾病的最新基因治疗进展,着重讨论了基于AAV载体和CRISPR/Cas9系统的基因治疗在NMD治疗中的潜在价值以及相应的风险。

Neuromuscular diseases(NMD)are a kind of central or nervous system diseases,mainly manifested by impaired motor units,reduced exercise endurance,and hypotonia.In the past several years,symptomatic treatment is the major therapy for NMD,which is able to relieves the symptoms.Adenoassociated virus vectors(AAV)are the most common tools,which are widely used in gene therapy and vaccine due to their safety,low immunogenicity and long expression time.More importantly,dividing and nondividing cells can be effectively infected with AAV.CRISPR/Cas9(CRISPR-associated protein 9),derived from typeⅡCRISPR(clustered regularly interspaced short palindromic repeats)bacterial immune systems,is emerging as a powerful tool for gene editing.It has the characteristics of precise targeting,low off-target rate,and low cytotoxicity.In this review,recent progress in gene therapy of several common NMD are summarized.The potential value and corresponding risks of gene therapy based on AAV vector and CRISPR/Cas9 system in the treatment of NMD are mainly discussed.