| 郭思达 周艳 姜春来.基于修饰CCR5基因的艾滋病基因治疗进展[J].,2014,14(22):4372-4373 |
| 基于修饰CCR5基因的艾滋病基因治疗进展 |
| Developing of CCR5 as Target for HIV-1 Gene Therapy |
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| DOI： |
| 中文关键词: 艾滋病 基因治疗 CCR5 基因 脐带血 |
| 英文关键词: AIDS Gene therapy CCR5 gene Cord blood |
| 基金项目:中央高校基本科研业务经费（201200003） |
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| 中文摘要: |
| 艾滋病药物治疗主要障碍是难以彻底清除病毒、副作用大、成本高且需长期用药。CCR5 是HIV 侵染的主要辅助受体，缺陷
型CCR5（CCR5△32）的CD4+T 细胞对R5 嗜性HIV-1 病毒感染有高度抵抗力。通过骨髓移植CCR5△32干细胞到患者体内可以
降低HIV 病毒载量至无法检出水平，同时可维持T 细胞数目在正常范围内。但由于CCR5△32 基因缺失的人群所占比例少、配型
困难等问题，CCR5△32 干细胞移植无法广泛用于艾滋病的临床治疗。通过锌指核酸酶(ZFNs)或类转录激活因子效应物核酸酶
(TALENs)两种方法可以将自体细胞CCR5 基因人为部分缺失，将产生的CCR5 缺陷细胞回输体内可阻断HIV-1 入侵途径，稳定
CD4 细胞群体并最终清除病毒。而脐带血干细胞具有对配型要求低等优点，使其作为修饰的靶细胞具有广阔的应用前景。 |
| 英文摘要: |
| The main obstacles to HIV eradication with highly active antiretroviral therapy (HAART) contain severe side effects
and high cost of treatment. The viral entry is mediated by specific interaction of the viral envelope (Env) glycoprotein with CCR5
co-recepter which is an endogenous chemokine receptor on CD4+T cells. Cells which are homozygosity for the CCR5△32 confer highly
resistance to HIV-1infection (R5 type). Bone marrow transplantayion from the homozygote CCR5△32 mutation to HIV-1 infected
patients can reduc HIV viral load to undetectable level and maintain CD4+T cell population. Because of the low rate of CCR5△32
mutation and difficult to matching, CCR5△32 defected hematopoietic stem cell transplantation cannot be widely used in AIDS clinical
treatment. However, using Zinc Finger Nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) to modify CCR5
gene and reinfuse into the body has shed a light on the HIV treatment strategies. It can resist the infection of CCR5-tropic HIV-1, stabilize
CD4+T-cell counts and finally eliminate HIV-1. Because cord blood stem cell transplantation has advantages such as lower requirements
of matching than bone marrow transplantation, thus makes it a target cell for gene modifying therapy with great application prospect. |
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