September #84 : Run Interference - by Mike Barr

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This Face has a Message for the World

Lines Composed in a Looking Glass

The Problem with Protease

Lipo: The Latest

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Run Interference

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Hepatitis & HIV


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September 2002

Run Interference

by Mike Barr

HIV's habit of invading your CD4 cells, commandeering the DNA to reproduce itself and then destroying the cells is what makes it such an annoying little critter, a.k.a. "an RNA-based retrovirus." Now researchers may have found a way to turn HIV's parasitic RNA against itself -- by using a new, engineered form of RNA that can trip up the delinquent retrovirus' breaking-and-entering act.

Phillip Sharp, MD, a Massachusetts Institute of Technology virologist who won the Nobel in 1993 for related work, has turned his attention to the possibility of using these "interfering RNAs" against HIV and other viral infections.

In lab studies with mouse cells, two interfering RNAs -- one designed to target CD4s, the other to target the HIV core protein p24 -- were both shown to disable HIV's infection system. Tests to aim at a third target, CCR5, a cell protein that functions as an HIV receptor, are also planned.

The interfering-RNA approach is similar to previous attempts at gene therapy -- they all seek to switch off, or bind to, specific genes necessary for viral production and proliferation. One such technique, "antisense" technology, burst onto the scene with great fanfare in the late '80s. But as with nearly all such gene machines, the main mystery with both antisense and interfering RNA remains how to coax the stuff into the desired cells in the body, a not-so-simple trick techies call "drug delivery."

Harvard's Judy Lieberman, MD, Sharp's collaborator, struck an optimistic note. If these successes in the lab can be repeated in live animals, she said, she'll be optimistic about one day using interfering RNAs to stop HIV replication in humans.

If this all sounds very future shock, it is. "There are many obstacles to surmount before this could be a basis for treatment," Sharp said, cautioning that an RNA-based med would be "several years off, at least." Meantime, triple cocktails will have to do.




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