Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5

• DOI: 10.1073/pnas.232688199
• Publication Date: 2003-01-07T17:22:42Z
• Authors: Xiao-Feng Qin; Dong Sung An; Irvin S. Y. Chen; David Baltimore
• Keywords: 0301 basic medicine; type-1; gene-therapy; Receptors, CCR5; receptor; T-Lymphocytes; Genetic Vectors; viral phenotype; in-vivo; Vesicular stomatitis Indiana virus; human-immunodeficiency-virus; intracellular immunization; 03 medical and health sciences; disease progression; 616; Humans; RNA, Small Interfering; Cells, Cultured; Acquired Immunodeficiency Syndrome; deletion allele; Lentivirus; 500; 3. Good health; macrophage-tropic HIV-1; CCR5 Receptor Antagonists; HIV-1; Caltech Library Services

Double-stranded RNAs ≈21 nucleotides long [small interfering RNA (siRNA)] are recognized as powerful reagents to reduce the expression of specific genes. To use them protect cells against viral infection, effective methods for introducing siRNAs into primary required. Here, we describe success in constructing a lentivirus-based vector introduce HIV-1 coreceptor, CCR5, human peripheral blood T lymphocytes. With high-titer stocks, >40% lymphocytes could be transduced, and potent CCR5-siRNA resulted up 10-fold inhibition CCR5 on cell surface over period 2 weeks absence selection. In contrast, another major CXCR4, was not affected. Importantly, blocking by provided substantial protection lymphocyte populations from CCR5-tropic virus dropping infected 3- 7-fold; only minimal effect infection CXCR4-tropic observed. Thus, our studies demonstrate feasibility potential lentiviral vector-mediated delivery general means intracellular immunization treatment other diseases.