Boden Daniel, Pusch Oliver, Ramratnam Bharat
Brown Medical School, Laboratory of Retrovirology, Division of Infectious Diseases, Department of Medicine, Providence, RI 02903, USA.
Curr Opin Mol Ther. 2004 Aug;6(4):373-80.
The preclinical development of RNA interference (RNAi) as a novel therapeutic agent for HIV-1 infection is reviewed. RNAi refers to the sequence-specific degradation of RNA that follows the cellular introduction of homologous, short-interfering RNA (siRNA). RNAi has emerged as a powerful tool to probe the function of genes of known sequence in vitro and in vivo. Advances in vector design permit the effective expression of siRNA in human cells by transfer of short hairpin RNA expression cassettes. Recent investigations have described the ability of RNAi to decrease the replication of HIV-1 in lymphocytic cells using siRNA targeting viral (eg, Tat, Gag and Rev) and host (eg, CCR5 and CD4) proteins. Can RNAi be used as a form of genetic therapy for HIV-1 and associated infections? There are numerous challenges associated with converting RNAi from a laboratory technique to an antiviral therapeutic. Recent research on the cellular delivery, antiviral durability and gene-silencing specificity of HIV-1-specific RNAi is reviewed.
本文综述了RNA干扰（RNAi）作为一种针对HIV-1感染的新型治疗药物的临床前开发情况。RNAi是指在细胞导入同源性短干扰RNA（siRNA）后，RNA发生序列特异性降解。RNAi已成为一种强大的工具，可在体外和体内探究已知序列基因的功能。载体设计的进展使得通过短发夹RNA表达盒的转移，能在人类细胞中有效表达siRNA。最近的研究描述了RNAi利用靶向病毒（如Tat、Gag和Rev）和宿主（如CCR5和CD4）蛋白的siRNA降低HIV-1在淋巴细胞中复制的能力。RNAi能否用作HIV-1及相关感染的基因治疗形式？将RNAi从实验室技术转化为抗病毒治疗存在诸多挑战。本文综述了近期关于HIV-1特异性RNAi的细胞递送、抗病毒持久性和基因沉默特异性的研究。
