ANTIVIRAL ACTIVITY OF LIPOSOMAL ANTISENSE OLIGONUCLEOTIDES

脂质体反义寡核苷酸的抗病毒活性

• 批准号: 3748271
• 负责人: M P SELVAM
• 金额: --
• 依托单位: BUREAU OF HEALTH PLANNING AND RESOURCES DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3748271
• 关键词: AIDS therapy; RNA directed DNA polymerase; antiAIDS agent; antisense nucleic acid; antiviral agents; antiviral antibody; human immunodeficiency virus 1; immunoconjugates; immunofluorescence technique; immunologic assay /test; liposomes; nucleic acid sequence; oligonucleotides; polymerase chain reaction; regulatory gene; tissue /cell culture; virus RNA; virus genetics; virus replication; western blottings

These sequence specific suppression of HIV -1 replication using HIV-1 antibody -targeted liposomes containing antise nse phosphorothioate oligonucleotides is described. Liposomes were generated, which encapsulated the 20 mer sequence of the rev HIV-1 regulatory gene in the form of a phosphorothioate oligonucleotide. Specific targeting was accomplished by conjugating purified HIV-1 posiThe sequence specific suppression of HIV-1 replication using HIV-1 antibody-targeted liposomes containing antisetive human IgG to the surface of the liposomes to form an immunoliposome. HIV-1-infected H9 cells incubated with the immunoliposomes were rendered less permissive for viral multiplication. As compared with the positive control infected with HIV-1, HIV-1 replication was reduced by nearly 95 percent in antisense immunoliposome treated cells. Inhibition of HIV-1 replication was not observed using empty or immunoliposomes containing random phosphorothioate oligomer sequences. These immunoliposomes exhibit dual specificity: a targeting antibody on the surface of the liposome specific for infected cells, and inside the immunoliposome, an oligomer with antiviral activity that is complementary to a specific portion of the mRNA of the infected cell. The antiviral activity of the free as well as the encapsulated oligonucleotides were assessed by p24, RT assays, Western Blot, immunofluorescence and PCR analysis. Liposome preparations demonstrated minimal toxicity in H9 cell culture experiments. The altered HIV-1 mRNA specifically induced by targeted antisense liposomes suggests that the mechanism for the inhibition of viral expression is its interaction with the rev regulatory gene resulting in translation arrest. These in vitro culture results demonstrate the potential efficacy of drug-encapsulating immunoliposomes in the treatment of AIDS and AIDS related infections.

这些序列特异性抑制HIV-1复制使用HIV-1