Rossi John J
Division of Molecular Biology, Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
Biotechniques. 2006 Apr;Suppl:25-9. doi: 10.2144/000112167.
Human immunodeficiency virus type 1 (HIV-1) was the first primate virus shown to be inhibited by RNA interference (RNAi). Early studies used both synthetic and promoter expressed small interfering RNAs (siRNAs) or expressed short hairpin RNAs (shRNAs) to demonstrate that this virus was susceptible to RNAi. In addition to targeting the virus itself RNAi-mediated down-regulation of cellular targets that encode receptors required for viral entry also proved to be effective. The power of RNAi as an anti-HIV agent has propelled development of RNAi-based gene therapy approaches for the treatment of HIV infection in humans. Nevertheless, extensive in vitro experimentation has revealed potential problems of viral escape mutants and other toxicities caused by the si/shRNAs. This review covers the progress and problems in the development of RNAi for the treatment of HIV infection. Potential modalities for clinical application of RNAi in the treatment of HIV-1 infection are also described.
1型人类免疫缺陷病毒（HIV-1）是首个被证明可被RNA干扰（RNAi）抑制的灵长类病毒。早期研究使用合成的和启动子表达的小干扰RNA（siRNA）或表达的短发夹RNA（shRNA）来证明这种病毒对RNAi敏感。除了靶向病毒本身外，RNAi介导的对编码病毒进入所需受体的细胞靶点的下调也被证明是有效的。RNAi作为一种抗HIV药物的强大作用推动了基于RNAi的基因治疗方法的发展，用于治疗人类的HIV感染。然而，广泛的体外实验揭示了病毒逃逸突变体和si/shRNA引起的其他毒性等潜在问题。本综述涵盖了RNAi治疗HIV感染研发过程中的进展和问题。还描述了RNAi在治疗HIV-1感染临床应用中的潜在模式。
