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HIV overcomes CRISPR gene-editing attack

nature.com

21–30 of 31 posts

Re: HIV overcomes CRISPR gene-editing attack

#22
post #2

With the caveat that I have only had this explained to me ... The one location in the HIV genome that consistently doesn't mutate is the hexamer boundary of the viral capsid. Seems like that would make a better taerget sequence as a result. Anyone here know why they chose the sequences that they did?

Is that area accessible to the enzymes. Not all parts of the stand are equally accessible.

Re: HIV overcomes CRISPR gene-editing attack

#23
post #20

Let's very pessimistically say this attack killed 50% of viruses, and only those lucky enough to have a mutation at the cleavage site managed to survive, and then multiply after, making the virus immune to that specific cleavage. Couldn't you then cleave at a few sites at once? With 64 different cleavage sites, only 1/2^64 viruses will survive, meaning it's pretty much completely certain you will kill every last viru…

I would bet that just kills all the cells. Actually, I'm still of the opinion that killing the cells containing a target sequence (and thus selecting for pre-existing mutants) accounts for a large portion of what has been published regarding this tech. Neither of these papers seem to report on that aspect. Figure S1A of the Cell paper shows cell counts before the HIV sequence was introduced, but they are silent on what happened after. Or did I miss it?

Re: HIV overcomes CRISPR gene-editing attack

#24

I wonder if it'd be possible to alter HIV into something benign instead of killing it. If done properly, that'd eliminate the virus's drive to out-evolve our treatment.

HIV is relatively benign. People love for years without showing symptoms, hence its success.

To beat that we'd have to find something which could deny it resources without killing the host (us). But that's pretty much just 'a cure'

Re: HIV overcomes CRISPR gene-editing attack

#25
post #20

Let's very pessimistically say this attack killed 50% of viruses, and only those lucky enough to have a mutation at the cleavage site managed to survive, and then multiply after, making the virus immune to that specific cleavage. Couldn't you then cleave at a few sites at once? With 64 different cleavage sites, only 1/2^64 viruses will survive, meaning it's pretty much completely certain you will kill every last viru…

From the article...

> Both he and Liang think that the problem can be surmounted, for instance by inactivating several essential HIV genes at once...

Re: HIV overcomes CRISPR gene-editing attack

#26
post #5

The biggest problem with HIV is that when you're dealing with one person with "HIV" you're actually fighting dozens of different adaptations of the virus, much like how cancer tumors differentiate into dozens of cell types. My approach would be to compare and contrast SIV and HIV defense strategies in humans and chimps. How does the TRIM5-alpha in chimps manage to fight off HIV, and how does human TRIM5-alpha fight o…

What makes you think that they aren't doing that already? That seems like the first thing anyone would think of doing.

Well, I keep up on my journal reading, and my sister's a medical doctor from Penn. The first serious proposal for preliminary trim5-alpha based gene therapy was released in 2015, without much reaction.

Some previous work has been done. Modified human T-cells with a copy of new world monkey trim5-alpha. The result was successful in vitro. I believe that was 2008.

My point was really, "Why doesn't this rather straightforward mechanism receive more time and research?"

*Disclaimer: I have worked in bioinformatics.

Re: HIV overcomes CRISPR gene-editing attack

#28
post #27

If every computer scientist studied medicine for the next 8 years I wonder how much that would increase the likelihood of finding an HIV cure?

What's with the attitude of "computer scientists can solve anything if they displace the original researchers who are incompetent"?

Re: HIV overcomes CRISPR gene-editing attack

#29
post #27

If every computer scientist studied medicine for the next 8 years I wonder how much that would increase the likelihood of finding an HIV cure?

Probably not really. At most you would get really efficient datasets about the virus. Maybe things like 'an algorithm that recognizes patterns in mutations to attempt a simulation of hiv resistance to various treatments'. Computer science could probably make the information available cute and neatly parsed but 8 years of medicine experience is baby-level.

Re: HIV overcomes CRISPR gene-editing attack

#30
post #26

Earlier quoted context omitted.

What makes you think that they aren't doing that already? That seems like the first thing anyone would think of doing.

Well, I keep up on my journal reading, and my sister's a medical doctor from Penn. The first serious proposal for preliminary trim5-alpha based gene therapy was released in 2015, without much reaction. Some previous work has been done. Modified human T-cells with a copy of new world monkey trim5-alpha. The result was successful in vitro. I believe that was 2008. My point was really, "Why doesn't this rather straightf…

Thank you. If that is indeed the case then I'm left asking the same question.
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