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210 Potential Use of Macrophage-Tropic DNA-Enzymes to Inhibit HIV-1 Gene Expression
A. C. Banerjea*
Natl. Inst. of Immunology, New Delhi, India
Background: HIV-1 replicates in a variety of host cells in humans and it is believed that macrophages are the reservoirs. Antiretroviral therapies have provided clear evidence that additional novel antiviral approaches are required that target the macrophages that harbor or support active replication of HIV-1.
Methods: We have exploited the recently described 10-23 catalytic motif containing DNA-enzymes to target the scavenger receptors present on macrophages by adding a poly-G tail at its 3 end.
Results: This poly-G tagged DNA-enzyme retained its ability to cleave HIV-1 TAT/Rev RNA in a sequence-specific manner and showed specific uptake by human macrophages in the complete absence of lipofectin. Furthermore, we found that DNA-enzyme treated cells interfered significantly with HIV-1 gene expression besides showing protection against the virus challenge.
Conclusions: Our strategy could be combined with other known antiretroviral approaches against HIV-1 and essentially could be used against any other pathogen that uses macrophages for its replication.
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