Ⅰ型神经纤维瘤病的基因治疗策略与前景  

Gene therapy strategies and prospects for neurofibromatosis type 1

作　　者：郑婷婷 朱倍瑶 王智超 李青峰[1,2] ZHENG Tingting;ZHU Beiyao;WANG Zhichao;LI Qingfeng(Department of Plastic and Reconstructive Surgery,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200011,P.R.China;Neurofibromatosis Type 1 Center,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200011,P.R.China)

机构地区：[1]上海交通大学医学院附属第九人民医院整复外科,上海200011 [2]上海交通大学医学院附属第九人民医院Ⅰ型神经纤维瘤病诊疗中心,上海200011

出　　处：《中国修复重建外科杂志》2024年第1期1-8,共8页Chinese Journal of Reparative and Reconstructive Surgery

基　　金：国家自然科学基金资助项目(82102344、82172228)。

摘　　要：目的总结Ⅰ型神经纤维瘤病(neurofibromatosis type 1,NF1)基因治疗策略和相关研究进展。方法查阅近年来国内外关于NF1基因治疗的文献,对NF1基因结构、功能及其突变进行分析,并从转基因治疗和基因编辑两方面对基因治疗策略进行深入总结。结果NF1是由抑癌基因NF1基因突变引起的常染色体显性遗传肿瘤性疾病,因神经纤维瘤蛋白功能受损而致病,临床表现复杂,目前尚无法根治。NF1的基因治疗策略仍处于研究和开发阶段。现有NF1转基因疗法主要是在神经纤维瘤蛋白缺陷的细胞中构建并表达Ras-GTP酶激活蛋白相关结构域基因片段,证实了NF1基因治疗的可行性;未来研究方向主要聚焦于使用拆分载体递送系统,增加单一载体的运载量,以及开发新的递送系统用于靶向递送全长NF1 cDNA。此外,新一代基因编辑工具在NF1等单基因遗传病的治疗领域应用潜力巨大,但效率和安全性尚需进一步验证。结论基因治疗,包括转基因和基因编辑两大技术,有望成为NF1患者重要的新型治疗手段。Objective To summarize the gene therapy strategies for neurofibromatosis type 1(NF1)and related research progress.Methods The recent literature on gene therapy for NF1 at home and abroad was reviewed.The structure and function of the NF1 gene and its mutations were analyzed,and the current status as well as future prospects of the transgenic therapy and gene editing strategies were summarized.Results NF1 is an autosomal dominantly inherited tumor predisposition syndrome caused by mutations in the NF1 tumor suppressor gene,which impair the function of the neurofibromin and lead to the disease.It has complex clinical manifestations and is not yet curable.Gene therapy strategies for NF1 are still in the research and development stage.Existing studies on the transgenic therapy for NF1 have mainly focused on the construction and expression of the GTPase-activating protein-related domain in cells that lack of functional neurofibromin,confirming the feasibility of the transgenic therapy for NF1.Future research may focus on split adeno-associated virus(AAV)gene delivery,oversized AAV gene delivery,and the development of new vectors for targeted delivery of full-length NF1 cDNA.In addition,the gene editing tools of the new generation have great potential to treat monogenic genetic diseases such as NF1,but need to be further validated in terms of efficiency and safety.Conclusion Gene therapy,including both the transgenic therapy and gene editing,is expected to become an important new therapeutic approach for NF1 patients.

关 键 词：型神经纤维瘤病 NF1基因 转基因治疗 基因编辑 

分 类 号：R596[医药卫生—内科学]