基因治疗慢病毒载体的转导增强策略<sup>*</sup>

doi:10.13523/j.cb.2104039

中国生物工程杂志

2021, Vol. 41

Issue (8): 52-58 DOI: 10.13523/j.cb.2104039

综述

基因治疗慢病毒载体的转导增强策略^*

赵晓煜¹,徐祺玲^1,²,赵晓东^2,^3,^4,^5,^**(

),安云飞^1,^2,^3,^4,⁵

1 重庆医科大学附属儿童医院重庆 400014
2 儿童感染免疫重庆市重点实验室重庆 400014
3 儿童发育疾病研究教育部重点实验室重庆 400014
4 国家儿童健康与疾病临床医学研究中心(重庆) 重庆 400014
5 儿童发育重大疾病国家国际科技合作基地重庆 400014

Enhancing Lentiviral Vector Transduction Efficiency for Facilitating Gene Therapy

ZHAO Xiao-yu¹,XU Qi-ling^1,²,ZHAO Xiao-dong^2,^3,^4,^5,^**(

),AN Yun-fei^1,^2,^3,^4,⁵

1 Department of Rheumatology and Immunology, Affiliated Children's Hospital of Chongqing Medical University, Chongqing 400014, China
2 Chongqing Key Laboratory of Children's Infection and Immunity, Chongqing 400014, China
3 Key Laboratory of Children's Developmental Diseases, Ministry of Education, Chongqing 400014, China
4 National Children's Health and Disease Clinical Medical Research Center (Chongqing), Chongqing 400014, China
5 National International Science and Technology Cooperation Base for Major Children's Developmental Diseases, Chongqing 400014, China

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摘要：

基于慢病毒载体的体外基因治疗已在临床试验中取得良好的效果,有望治愈一些造血系统的单基因遗传病。通过提高靶细胞转导效率和减少转导中病毒载体量,基因治疗有效性、安全性和成本都可以得到改善。不同包膜糖蛋白伪型慢病毒载体通过与细胞膜表面的不同受体结合,促进病毒黏附和入胞,增强不同靶细胞的病毒转导效率。此外病毒转导增强剂可以在病毒进入细胞过程或进入后发挥作用,在提高转导效率的同时使靶转导基因在体内长期稳定表达。通过对这两类方法的总结回顾,旨在为慢病毒载体的转导效率提供新的优化策略,使基因治疗得到更广泛的应用。

关键词： 基因治疗; 转导效率; 慢病毒载体; 包膜糖蛋白; 病毒转导增强剂

Abstract:

Lentiviral vectors (LVVs) are used for various gene therapeutic applications in vitro, and have shown very promising results in several clinical trials. This possibility of a durable cure for monogenic diseases affecting the hematopoietic system has made gene therapy very attractive. Yet, efficiency, safety, and cost of LVVs gene therapy could be ameliorated by enhancing target cell transduction levels and reducing the amount of LVVs used on the cells. LVVs are pseudotyped with different viral envelope glycoproteins to alter and improve their tropism for different target cells. Another strategy to optimize the entry and post-entry steps of LVVs is the addition of transduction enhancers (TEs) during the transduction procedure, which improves the transduction efficiency and keeps stable expression of transferred genes in vivo. The combination of pseudotyping with heterologous viral envelopes and adding TEs increased the transduction efficiency of LVVs, and has the potential to improve clinical protocols.

Key words: Gene therapy Transduction efficiency Lentiviral vectors Envelope glycoprotein Viral transduction enhancer

收稿日期: 2021-04-22 出版日期: 2021-08-31

ZTFLH:

Q812

基金资助: * 重庆市科技计划资助项目(cstc2018jscx-msybX0005)

通讯作者: 赵晓东 E-mail: zhaoxd530@aliyun.com

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引用本文:

赵晓煜,徐祺玲,赵晓东,安云飞. 基因治疗慢病毒载体的转导增强策略^*[J]. 中国生物工程杂志, 2021, 41(8): 52-58.

ZHAO Xiao-yu,XU Qi-ling,ZHAO Xiao-dong,AN Yun-fei. Enhancing Lentiviral Vector Transduction Efficiency for Facilitating Gene Therapy. China Biotechnology, 2021, 41(8): 52-58.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2104039 或 https://manu60.magtech.com.cn/biotech/CN/Y2021/V41/I8/52

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