Im sure you all remember the guy I wrote about a while back, who had HIV-1 and leukemia. While that is actually pretty common, what wasnt common was his treatment– a bone marrow transplant from a match who happened to lack the CCR5 gene, thus lacked one of the co-receptors HIV-1 needs to infect cells. This was a death-blow to the HIV-1 in this guys system. The virus in him simply has no (or very few) place else to go, so it burned out.
But this is simply a non-viable idea for ‘curing HIV/AIDS’ for basically everyone else on the planet. Financial barriers, technological barriers, immunological/genetic barriers (not enough people who are delta-CCR5, certainly not enough have the genetic diversity to be an appropriate match for everyone with HIV-1).
A new idea has come up that doesnt help with the first two problems (but technology does get cheaper over time), but it helps with the last problem– What if we could make any bone marrow donor delta-CCR5?
How this would theoretically work:
1. Find an appropriate genetic bone marrow match for the HIV-1+ patient, OR, get bone marrow from the patient him/herself (though some say bone marrow is infectable with HIV-1, so this might not be possible)
2. Treat the bone marrow with a lentivirus that contains an MLV promoter for an anti-CCR5 gene
3. Bone marrow transplant to HIV-1+ patient
4. The bone marrow will generate new immune cells.
5. The new immune cells are genetically modified by the viral vector to express the anti-sense CCR5 RNA, which will bind to the normal CCR5 mRNA. This double-stranded RNA PISSES OFF the cell, so it destroys it. Thus CCR5 mRNA is never translated into CCR5 proteins. The person is functionally, if not genetically, deltaCCR5.
Of course, things really arent that straight forward. Bone marrow transplants arent a casual deal– over 10% of the people who get them die from complications. You cannot get one unless its life-or-death, and if youve got HIV-1 thats under control with meds, you arent gonna get one– Just people with HIV-1 AND leukemia/lymphoma.
And then theres the gene therapy side of it. MLV has a great promoter we can pirate to get the anti-CCR5 RNA made, and it knows to keep its mouth shut in the pluripotent state, so their wayward gene expression doesnt screw up the normal development of various cell types… but it causes… leukemia and lymphomas (except when it doesnt). But lentiviral vectors have some advantages over MLV. So they cut/pasted a lentivirus with the MLV promoter with the anti-CCR5 message (previous post on cutting/pasting viruses together to make better gene therapy vectors).
And, everything in this paper is in culture dishes. Not people, yet. What if the stem cells (or their progeny) just quit making the anti-CCR5 message? Does that happen in one year in people? One month? Ten years? We dunno. We dont really know what controls latency in regular retroviruses yet, certainly not ones we are screwing around with. Nothing would be as disappointing as going through this ordeal, surviving it, thinking youre ‘cured’, and things go to shit again in a few months/years.
But as far as tissue culture work goes, this is nice. And even if we cant ultimately use it for HIV-1, we might be able to use the technology these folks are working on for any number of diseases.