多囊肾病的基因治疗进展  

Research progress of gene therapy in polycystic kidney disease

作　　者：李馨茗 毛志国 梅长林 薛澄 Li Xinming;Mao Zhiguo;Mei Changlin;Xue Cheng(Department of Nephrology,the Second Affiliated Hospital of Naval Medical University,Shanghai Changzheng Hospital,Shanghai 200003,China)

机构地区：[1]海军军医大学第二附属医院(上海长征医院)肾内科,解放军肾脏病研究所,上海200003

出　　处：《中华肾脏病杂志》2024年第11期905-911,共7页Chinese Journal of Nephrology

摘　　要：多囊肾病(polycystic kidney disease,PKD)是一种遗传性肾脏疾病,以肾脏形成大量囊肿、随着时间推移损害肾功能为特征。它主要分为常染色体显性多囊肾病(autosomal dominant polycystic kidney disease,ADPKD)和常染色体隐性多囊肾病(autosomal recessive polycystic kidney disease,ARPKD)两种类型,其中ADPKD更为常见。目前对于PKD的治疗主要集中在缓解症状和延缓病程,尚缺乏根治方法。但是,基因编辑技术如成簇规律间隔短回文重复序列(clustered regularly interspaced short palindromic repeats,CRISPR)及其关联蛋白9(CRISPR-associated protein 9,CRISPR-Cas9)和腺相关病毒载体的发展,为ADPKD和ARPKD的治疗提供了潜在的可能性。反义寡核苷酸治疗、腺病毒介导的基因敲低、CRISPR-Cas9、Pkd1基因增强疗法以及诱导多能干细胞等,在动物模型和早期临床研究中均展示了潜在疗效。尽管存在技术挑战、伦理法律问题及高成本的问题,基因治疗仍然为PKD治疗带来前所未有的希望,期待未来多学科合作和国际合作能为PKD患者提供更有效的治疗策略。Polycystic kidney disease(PKD)is a hereditary kidney disease characterized by the formation of numerous cysts in the kidneys,which progressively impairs renal function over time.PKD is primarily divided into two types:autosomal dominant polycystic kidney disease(ADPKD)and autosomal recessive polycystic kidney disease(ARPKD),with ADPKD being more prevalent.Current treatments primarily focus on symptom relief and disease progression delay,lacking a curative approach.However,the development of gene editing technologies such as clustered regularly interspaced short palindromic repeats(CRISPR)and CRISPR-associated protein 9(CRISPR-Cas9)and adeno-associated virus(AAV)vectors has offered new therapeutic possibilities for ADPKD and ARPKD.These include approaches like antisense oligonucleotides(ASO),adenovirus-mediated gene knockdown,CRISPR-Cas9,Pkd1 gene enhancement therapy,and the use of induced pluripotent stem cells(iPSCs),which have shown potential efficacy in animal models and early clinical studies.Despite facing technological challenges,ethical and legal issues,and high costs,gene therapy presents an unprecedented hope for PKD treatment.Future interdisciplinary collaboration and international cooperation are essential for developing more effective treatment strategies for PKD patients.

关 键 词：多囊肾疾病 基因治疗 寡核苷酸类 反义 CRISPR-Cas9 腺相关病毒载体 

分 类 号：R692[医药卫生—泌尿科学]