Yu M, Poeschla E, Wong-Staal F
Department of Medicine, University of California, San Diego, La Jolla 92093-0665, USA.
Gene Ther. 1994 Jan;1(1):13-26.
The retroviral life cycle and genetic plasticity of human immunodeficiency virus 1 (HIV-1) present unprecedented therapeutic challenges. Twelve years into the HIV epidemic, satisfactory treatment remains elusive. Our current understanding of AIDS pathogenesis calls for early intervention with antiviral agents. Although still in its infancy, human gene therapy holds considerable potential for the long-term treatment of genetic disorders, cancer and chronic infectious diseases. Gene therapy for HIV infection is receiving particularly intensive study: approaches that are in development include both immunotherapy (e.g. therapeutic vaccines and adoptive transfer of CD8+ T-cell clones) and direct antiviral therapy (intracellular immunization). The latter strategies include transdominant modifications of HIV proteins, RNA decoys, antisense RNA, ribozymes and modifications of cellular proteins (e.g. intracellular antibodies, soluble CD4). Several of these strategies are now entering clinical trials. While significant conceptual and technical hurdles remain to be overcome before the promise of gene therapy for HIV infection can be fully realized, progress in this field is likely to be rapid and to contribute to the broader applicability of human gene therapy to the treatment of other disorders.
人类免疫缺陷病毒1型（HIV-1）的逆转录病毒生命周期和基因可塑性带来了前所未有的治疗挑战。艾滋病流行已过去十二年，但仍难以实现令人满意的治疗效果。我们目前对艾滋病发病机制的理解要求使用抗病毒药物进行早期干预。尽管人类基因治疗仍处于起步阶段，但它在治疗遗传性疾病、癌症和慢性传染病方面具有巨大潜力。针对HIV感染的基因治疗正在进行特别深入的研究：正在开发的方法包括免疫疗法（如治疗性疫苗和CD8+T细胞克隆的过继转移）和直接抗病毒疗法（细胞内免疫）。后一种策略包括对HIV蛋白进行显性负性修饰、RNA诱饵、反义RNA、核酶以及对细胞蛋白进行修饰（如细胞内抗体、可溶性CD4）。其中一些策略现已进入临床试验阶段。尽管在HIV感染基因治疗的前景完全实现之前，仍有重大的概念和技术障碍有待克服，但该领域的进展可能会很快，并有助于人类基因治疗更广泛地应用于其他疾病的治疗。
