Kim Sang-Soo, Subramanya Sandesh, Peer Dan, Shimaoka Motomu, Shankar Premlata
Department of Biomedical Sciences, Center of Excellence for Infectious Diseases, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
Methods Mol Biol. 2011;721:339-53. doi: 10.1007/978-1-61779-037-9_21.
RNA interference (RNAi) is a potent and specific gene silencing mechanism that utilizes small -double-stranded RNA intermediates (small interfering RNAs or siRNAs) to target homologous mRNA sequences for degradation. The therapeutic potential of RNAi for HIV infection has been demonstrated in many studies. However, successful clinical application of RNAi is contingent on developing practical strategies to deliver siRNA to the desired target cells and tissues. Recently, there has been significant progress towards developing reagents that selectively deliver exogenous siRNA to immune cells that are targeted by HIV or involved in viral pathogenesis, such as T cells, macrophages, and dendritic cells. Here, we describe details of two antibody-based strategies for systemic delivery of siRNA either specifically to T cells via the CD7 receptor or to multiple immune cell types via LFA-1, present on all leukocytes.
RNA干扰(RNAi)是一种强大且特异的基因沉默机制,它利用小双链RNA中间体(小干扰RNA或siRNA)靶向同源mRNA序列进行降解。RNAi在治疗HIV感染方面的潜力已在许多研究中得到证实。然而,RNAi的成功临床应用取决于开发将siRNA递送至所需靶细胞和组织的实用策略。最近,在开发能够将外源性siRNA选择性递送至被HIV靶向或参与病毒发病机制的免疫细胞(如T细胞、巨噬细胞和树突状细胞)的试剂方面取得了重大进展。在此,我们描述了两种基于抗体的策略的细节,这两种策略可通过CD7受体将siRNA特异性地全身递送至T细胞,或通过存在于所有白细胞上的淋巴细胞功能相关抗原-1(LFA-1)将siRNA递送至多种免疫细胞类型。