Gene therapy might hold out hope for AIDS immunity

[Justforfun000]

This is a particularly novel approach. What I wonder is whether having enough T-cells that stay uninfected is enough to completely protect you from HIV. It SEEMS to make sense as years and years pass with no ill effect until the cd4's drop too low. Guess we'll have to hope this works in humans first.

http://blog.wired.com/wiredscience/2008 ... ng-co.html

Gene Editing Could Make Anyone Immune to AIDS
By Aaron Rowe EmailJune 30, 2008 | 5:16:56 PMCategories: Biotechnology, Chem Lab, Disease


Some people have a mutation that makes them amazingly resistant to HIV -- and now, scientists may have found a way to give that immunity to anyone.

Viruses enter cells and take them over, but to get inside, they need a handhold. HIV pulls itself in by grabbing onto a protein called CCR5, which decorates the surface of T-cells, which are one of the two major types of white blood cells and play an important role in helping the body fight infections. Back in the 1990's, researchers took interest in a handful of promiscuous gay men who were able to engage in sexual relations with their HIV-positive partners with impunity. Most of them had a mutation that kept their cells from producing normal CCR5 protein.

Armed with that knowledge, scientists have developed several tactics to block the production of CCR5 or perturb its shape so that the HIV virus can't grab onto it during the first step of its hijacking attempt. The strategy is much akin to cutting your hair before a wrestling match: It gives your opponent one less thing to grab onto.

In the latest version of this defense, Carl June and his colleagues at the University of Pennsylvania used a highly engineered protein, called a zinc finger nuclease, to clip the CCR5 gene out of some T-cells. Left without the recipe for that protein, the cells are nearly impenetrable. His report appeared on the Nature Biotechnology website yesterday.

June tested the procedure on cultured T-cells and mice -- not humans -- so it should be a source of guarded optimism, because it's not certain the technique would work in humans. In theory, AIDS doctors could take some T-cells out of an infected person, edit their genomes, and stick them back into their patient. Once they have returned to the body, each resistant cell will thrive and multiply in spite of the disease. This trick would not eliminate the virus, but it might be able to permanently raise the T-cell counts of AIDS patients, increasing their ability to resist secondary infections and remain healthy.

[Zixinus]

Interesting. What does this CCR5 protein do anyway? Won't it cause problems if you remove it?

[Justforfun000]

Interesting. What does this CCR5 protein do anyway? Won't it cause problems if you remove it?

From what I've read, it doesn't seem to have any effect in comparison to people who lack it. That's how they put it, some I'm not sure if it has any known function.

[Fire Fly]

The gene CCR5 encodes for a cell surface protein that is found on white blood cells and the CCR5 protein is used by HIV-1 (there exists also HIV-2) as a coreceptor (CXCR4 is the other receptor). HIV needs to bind to various receptors on the cell surface in order to inject its package. There's an allele of CCR5 that has a 32 base pair deletion, making the gene product shortened and nonfunctional. The CCR5 allele has actually been known for a long time now. In fact, people have found that individuals who have two functional copies of CCR5 are highly susceptible to infect, individuals with one functional and one non-functional copy are susceptible but progress to AIDS slowly, and people who have two non-functional copies of CCR5 are resistant to most strains.

Here's some data by Martinson et al. 1997 showing how frequent this allele appears in various populations around the world:



We have the population group, the size of the sample, the number of people in the sample size who had two functional copies of CCR5 (+/+), the number of people who had one functional and one non-functional copy ((+/delta-32), the number of people who had two non-functional copies, and the frequency at which each functional and non-functional allele appears in the entire sample. As you can see, Ashkenazi Jews, Icelanders, and Britons are unusually resistant to HIV-1 since their populations have a rather high frequency of the non-functional copy of CCR5.

So as you can see, if the allele appears in at a high percentage, it usually means that there has been inbreeding over time, resulting in an accumulation of the allele. This happens a lot when you have isolated populations due to geography or culture.

[Fire Fly]

There's a misspelling in the chart: it should read CCR5, not CCRD in the last column.

[Fire Fly]

I should also add that people shouldn't hold their breaths for this; gene therapy has had a rather bad success record.

[Admiral Valdemar]

I should also add that people shouldn't hold their breaths for this; gene therapy has had a rather bad success record.

Yeah, may want to ask those guys in France how they "cured" bubble boy syndrome.

I'm sure the termination of vital signals from a patient can cure anything, 'cept death.