心血管疾病的基因治疗

Gene therapy for cardiovascular disease

基因治疗在先天遗传性以及后天获得性心血管疾病治疗中均具有广阔的发展前景.对心血管疾病致病机理的深入认识和疾病基因组学研究的发展,进一步促进了临床前基因治疗的研究进展.但基因治疗过程中存在的机体细胞免疫反应、外源基因表达水平不足、在体基因转导效率低下等因素都成为基因治疗临床应用转化的瓶颈.近年来,基因导入载体和基因组编辑技术的发展为上述问题的改善和解决提供了新的思路.目前成族规律间隔短回文重复序列(clustered regularly interspaced short palindromic repeats,CRISPR)/Cas9基因组编辑技术已经成功应用于动物模型的在体基因编辑,达到了显著改善血脂指标的疗效.进一步研究体内组织特异和高效的基因导入方式,提高基因编辑的靶向效率和特异性,并建立全面有效的安全评估实验体系,将推动基因治疗向临床应用的转化.针对心血管疾病基因治疗中基因导入载体的研究以及CRISPR/Cas9基因组编辑技术的应用展开讨论.

Gene therapy shows great promise in the treatment of both inherited and acquired cardiovascular diseases. Identification of key molecule players in pathophysiology of cardiovascular disease and development of human disease genomic research lead to encouraging preclinical gene therapy studies in animal models. However, the presence of cellular immune responses, insufficient gene expression level and overall limited in vivo gene transduction efficiencies have hampered the translational progress to clinical use of gene therapy. In recent years, improvements in gene delivery system and discovery of advanced genome editing technologies open new therapeutic perspectives, with clustered regularly interspaced short palindromic repeats （CRISRP）/Cas9 genome editing technology already being successfully used in animal models to treat hypercholesterolemia. Further improvement in gene delivery efficiency, increase in targeting specificity of genome editing tools, and establishment of experimental systems for a thorough analysis of potential safety prob- lems would help eventually bring gene therapy recent advances in the use of different delivery for heart disease to reality. In this review, vectors and CRISPR/Cas9 genome editing technology in gene therapy research to treat cardiovascular diseases are discussed.