RNAi screening finds 273 proteins used by HIV
Harvard Medical School's Dr. Stephen J. Elledge and a team of scientists used RNA interference to screen thousands of protein-making genes, and have identified 273 proteins HIV needs in order to survive in human cells. The finding raises the possibility that the proteins may be targets for the treatment of AIDS. Previously, only 36 of proteins were known to play a role in HIV's survival.
Patients using current treatments often have to switch drug regimens as the virus mutates and becomes immune to older drugs. A therapy based on these new findings wouldn't have that same problem, since it would block the disease from entering human cells entirely. However, according to a Harvard press release, "the challenge will be to develop drugs that inhibit HIV by interacting with these human proteins without hurting our cells." Currently, only one drug prevents the virus from entering white blood cells--Pfizer's recently-approved Selzentry. The Harvard study was published in Science Magazine.
- see this press release on the findings
- read the New York Times article for more
Related Articles:
New HIV drugs offer breakthrough therapies. Report
Selzentry approval marks big win for Pfizer. Report
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By Anonymous | Posted 4:36pm | January 11, 2008
Currently, only one drug prevents the virus from entering white blood cells--Pfizer's recently-approved Selzentry.
What about Trimeris's FUZEON?
By David Rasnick | Posted 8:15am | January 14, 2008
I was surprised to learn the Harvard study led by Professor Stephen Elledge was conducted in highly aneuploid "HeLa-derived TZM-bl cells". I've worked the past 11 years studying the consequences of aneuploidy and feel I should pass along some of my concerns about the study's experiments and the authors' conclusions.
As I say, HeLa cells are massively aneuploid cervical cancer cells from the 1950s, containing typically 76-80 chromosomes and 22-25 abnormal chromosomes per cell instead of the normal complement of 46 (Macville M, Schrock E, Padilla-Nash H, Keck C, Ghadimi BM, Zimonjic D, Popescu N, Ried T: Comprehensive and definitive molecular cytogenetic characterization of HeLa cells by spectral karyotyping. Cancer Res 1999, 59:141-150).
No two HeLa cells are genetically alike, in fact no two use the same network of genes, gene products, transcription factors, receptors, etc. Furthermore, the HeLa cells are highly genomically unstable; they change with each cell division.
Thus, the claimed "273 proteins that the AIDS virus needs to survive in human cells" are probably an artifact of performing the experiments in the HeLa cells and actually have little or nothing to do with what goes on in people.
Ultimately, the multi-million dollar question is even if one can prevent HIV from replicating in HeLa cells by removing the susceptible human proteins, will the same thing happen in normal human cells in patients? The odds are strongly against it.
There is also the conceptual problem of administering drugs against human proteins since these drugs will be inherently toxic. I was in the drug design and development business for 20 years. The first principle in coming up with drugs against infectious agents was to target proteins specific to the pathogen and not human in order to minimize potential and actual toxic consequences.
Researchers should ponder these questions before going down the very expensive road suggested by the Harvard group.
Sincerely,
David Rasnick, PhD
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