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posted by chromas on Wednesday July 03 2019, @04:45PM   Printer-friendly
from the crisper-mice-now-with-crystals dept.

CRISPR and LASER ART Eliminate HIV from Mice

Today, a paper in Nature Communications, titled "Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice" [open, DOI: 10.1038/s41467-019-10366-y] [DX] reports new work from a collaborative effort showing that a combination of long-acting slow-effective release antiviral therapy (LASER) and CRISPR-Cas9 successfully cleared HIV from infected humanized mice.

Howard Gendelman, MD, professor of internal medicine and infectious diseases at the University of Nebraska Medical Center and senior author on the paper, does not withhold his excitement over the result, which may the reason for his hyperbole. He tells GEN that the conclusion is "almost unbelievable, but, it's true" an idea, he adds, that "has been science fiction up until now." He notes that "for the first time in the world" they have shown total elimination of HIV infection from a model with an established infection and, even though there are caveats, "there is a real possibility that an HIV cure can be realized."

The team used a technique developed by co-author Kamel Khalili, PhD, professor in the department of neuroscience at the School of Medicine at Temple University, that uses the CRISPR-Cas9 system to remove the integrated HIV DNA from genomes. They combined the genome editing technique with the LASER ART, a technique developed by Gendelman's lab that targets viral sanctuaries by packaging the ART drugs into nanocrystals. LASER ART distributes the drugs to areas of the body where HIV harbors and releases them slowly over time. Testing the combination of these two methods together in mice led the authors to conclude that permanent elimination of HIV is possible.

[...] Gendelman explains that "It's kind of like being in a beach and trying to find the right shell—you might want a certain color or shape." When HIV replicates, he says, there are "billions and trillions" of particles so you're asking CRISPR to excise every single DNA provirus in this morass. He adds, "it would be inconceivable that it would be efficient enough to destroy every DNA molecule.... If one infectious particle remains, it will grow and replicate. You have to destroy every single one in the body." So, the ART reduced the viable targets. If you are inhibiting viral replication, he explains, you reduce the amount of HIV DNA in the host—in the cells and in the body, and that allows the CRISPR to be more effective. "It's a numbers game," Gendelman notes.

But, efficiency is not the only problem in the relationship between CRISPR and HIV. The sequence specificity of the approach a double-edged sword, notes Coffin. On the one hand, it minimizes off-target effects. But, as Coffin explains, it also sets the stage for rapid selection of resistance. In a virus that mutates as rapidly as HIV, the changes could quickly render CRISPR useless. Lastly, the mice were infected with a clonal virus with CRISPR delivered shortly after the infection, leaving little opportunity to generate a diverse population. However, this is not analogous to human patients as most patients do not report for treatment so soon after an infection. An effective treatment for humans would have to be designed to treat diverse viral populations with lots of mutations.

Also at ScienceAlert, CBS, and CNBC.


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  • (Score: 0) by Anonymous Coward on Thursday July 04 2019, @05:39AM (1 child)

    by Anonymous Coward on Thursday July 04 2019, @05:39AM (#863040)

    ...from infected humanized mice

    The mind simply reels.

    (RIP MDC!)

  • (Score: 2) by takyon on Thursday July 04 2019, @06:05AM

    by takyon (881) <reversethis-{gro ... s} {ta} {noykat}> on Thursday July 04 2019, @06:05AM (#863042) Journal

    The mind simply reels.

    Tell that to the infected mice.

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