期刊
OLIGONUCLEOTIDES
卷 18, 期 4, 页码 329-335出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/oli.2008.0152
关键词
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资金
- IH/NIAID [AI042520]
Anti-human immunodeficiency virus-1 (HIV-1) polyamide (peptide) nucleic acids (PNAs) conjugated with cell-penetrating peptides (CPPs) targeted to the viral genome are potent virucidal and antiviral agents. Earlier, we have shown that the anti-HIV-1 PNA(TAR)-penetratin conjugate is rapidly taken up by cells and is nontoxic to mice when administered at repeat doses of as high as 100 mg/kg body weight. In the present studies we demonstrate that naked PNA(TAR) is immunologically inert as judged by the proliferation responses of splenocytes and lymph node cells from PNA(TAR)-immunized mice challenged with the immunizing antigen. In contrast, PNA(TAR)-penetratin conjugate is moderately immunogenic mainly due to its penetratin peptide component. Cytokine secretion profiles of the lymph node cells from the conjugate-immunized mice showed marginally elevated levels of proinflammatory cytokines, which are known to promote proliferation of T lymphocytes. Since the candidate compound, PNA(TAR)-penetratin conjugate displays potent virucidal and antiviral activities against HIV-1, the favorable immunological response together with negligible toxicity suggest a strong therapeutic potential for this class of compounds.
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