心血管疾病的基因治疗:基础研究与临床前景
Gene Therapy for Cardiovascular Disease: Basic Research and Clinical Prospects.
作者信息
Cao Genmao, Xuan Xuezhen, Zhang Ruijing, Hu Jie, Dong Honglin
机构信息
Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, China.
Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
出版信息
Front Cardiovasc Med. 2021 Nov 5;8:760140. doi: 10.3389/fcvm.2021.760140. eCollection 2021.
In recent years, the vital role of genetic factors in human diseases have been widely recognized by scholars with the deepening of life science research, accompanied by the rapid development of gene-editing technology. In early years, scientists used homologous recombination technology to establish gene knock-out and gene knock-in animal models, and then appeared the second-generation gene-editing technology zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) that relied on nucleic acid binding proteins and endonucleases and the third-generation gene-editing technology that functioned through protein-nucleic acids complexes-CRISPR/Cas9 system. This holds another promise for refractory diseases and genetic diseases. Cardiovascular disease (CVD) has always been the focus of clinical and basic research because of its high incidence and high disability rate, which seriously affects the long-term survival and quality of life of patients. Because some inherited cardiovascular diseases do not respond well to drug and surgical treatment, researchers are trying to use rapidly developing genetic techniques to develop initial attempts. However, significant obstacles to clinical application of gene therapy still exists, such as insufficient understanding of the nature of cardiovascular disease, limitations of genetic technology, or ethical concerns. This review mainly introduces the types and mechanisms of gene-editing techniques, ethical concerns of gene therapy, the application of gene therapy in atherosclerosis and inheritable cardiovascular diseases, in-stent restenosis, and delivering systems.
近年来,随着生命科学研究的深入以及基因编辑技术的迅速发展,遗传因素在人类疾病中的重要作用已得到学者们的广泛认可。早年,科学家们使用同源重组技术建立基因敲除和基因敲入动物模型,随后出现了依赖核酸结合蛋白和核酸内切酶的第二代基因编辑技术锌指核酸酶(ZFNs)和转录激活样效应物核酸酶(TALENs),以及通过蛋白质 - 核酸复合物发挥作用的第三代基因编辑技术——CRISPR/Cas9系统。这为难治性疾病和遗传性疾病带来了新的希望。心血管疾病(CVD)因其高发病率和高致残率一直是临床和基础研究的重点,严重影响患者的长期生存和生活质量。由于一些遗传性心血管疾病对药物和手术治疗反应不佳,研究人员正试图利用快速发展的基因技术进行初步尝试。然而,基因治疗临床应用仍存在重大障碍,如对心血管疾病本质认识不足、基因技术的局限性或伦理问题等。本文综述主要介绍了基因编辑技术的类型和作用机制、基因治疗的伦理问题、基因治疗在动脉粥样硬化和遗传性心血管疾病、支架内再狭窄以及递送系统中的应用。