HIV in cell culture can be completely eliminated using CRISPR-Cas gene editing [pdf]
escmid.org
escmid.org
Doesn't help people now, but may eliminate it as a threat for future generations.
There's research going with certain types of cancer where the doses of cancer-killing drugs isn't intended to eradicate all cancer cells, but to keep it at a level that's manageable with future treatments.
The theory being that if you go too far, cells that are left with a "lucky" mutation can grow without competition, leaving the patient in an even-less treatable state down the line.
The HIV genome is small and I would be surprised if it were so easy for such a thing to come about.
(This is an active research area I've read about in cancer treatment, where it's been suggested that being too aggressive with clearing certain cancers encourages reservoirs of already mutated aggressive variants to be unleashed after treatment whereas before the avenues they had to spread were already infected with the less aggressive variant).
Evolutionary pressure is present in any situation and is unavoidable. It still has an effect even in cases where treatments are effective with a success rate of 100%: the selection of diseases for which there is no cure.
Entertaining such a perspective can lead to an extreme and undesirable conclusion, that the only logical outcome is to do nothing and dismantle the entire modern medical practice.
It's not very constructive.
>It's not very constructive. >Entertaining such a perspective can lead to an extreme and undesirable conclusion, that the only logical outcome is to do nothing and dismantle the entire modern medical practice.
Disagree, if you read my parent comment in this thread, I talk about the research going on in cancer to account for evolutionary pressure, and the conclusion they arrived at is nowhere near "do nothing".
It is instead a change in treatment protocols to aim for less aggressive treatment, the clinic in questions motto is for the patients to die from something other than their cancer by having them on a protocol that has them live permanently with their cancer under the thesis that aggressrive attempts at eradication risk a stronger variant resurging.
Obviously it's not applicabale for all types of cancer which is why it's research, and why I'm not telling anyone that evolutionary pressure is a concern here, but am simply asking the question to learn if there are similar concerns between cancer and hiv disease treatments.
Generally the viral load of a patient with HIV is miniscule but must always be kept in check.
Note that the point of a crispr treatment is that it would delete dormant HIV sequences that are hiding in the host DNA and not currently producing virii but threatening to pop up at some time in the future.
Obviously this too is subject to evolutionary pressures but almost certainly not the ones you are thinking of.
> This press release is based on abstracts P0004 P0006, P0013, P0026 and P0004 at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID). The material has been peer reviewed by the congress selection committee. Only material from P0004 has been published in a preprint article. The other three have not yet been submitted to a medical journal or as preprints.
Basically, what's needed to commercialize this?
1. https://www.fda.gov/news-events/press-announcements/fda-appr...
Frankly just getting it to work at all is the real hurdle in this case.
At this point do we know every gene that had the potential to cause cancer?
The problem with CRISPR is that we cannot control where the off-target effects happen, we can currently only optimise the guiding RNA and the Cas enzyme to have as little off-target effects as possible (but not 0, yet). It would be cool to engineer guiding RNAs that bind in those high mutation-rate areas when they have off-target effects, stuff can mutate there and nothing will happen (probably).
This being the point. Many diseases have been cured dozens of times over in a tissue sample in a lab that never make it to actual therapies because the hurdle is elsewhere. The risks with crispr are as stated, especially flooding your entire body with it to target a virus.
There are more recent techniques, notably prime editing, that use a modified version of the CRISPR system that can introduce changes to single bases (nucleotides) in the genome. These have some promise of directly fixing diseases caused by single mutations, but there are hurdles in terms of efficiently delivering the prime editor to the right tissues as well as efficiency of the actual repair.
- Delivery: getting the mRNA and guide RNA into the target cells
- Expression: ensuring the target cell expresses the mRNA, thus making the protein
- On Target Editing Efficiency: ensuring the intended edit happens at a high rate
- Off Target Editing: ensuring other edits in other locations do not occur
"Sickle Cell Disease Approvals Include First CRISPR Gene Editing Therapy"
https://jamanetwork.com/journals/jama/article-abstract/28137....
- Blood stem cells are removed from the patient and the CRISPR Cas9 protein outside of the body is injected to cut the gene responsible for suppressing fetal hemoglobin production (even people with sickle cell have healthy fetal hemoglobin, their adult hemoglobin gene is what causes the deformed red blood cells)
- Chemotherapy is used to kill all living bone marrow and remove all previous unedited stem cells.
- New edited stem cells are inserted, and patient recovers with new blood production being of healthy red blood cells.
I'd say a huge step forward was FDA and EMA approval, but figuring out a way to remove previous unedited stem cells with chemotherapy would be a step change in the patient experience.
- New edited stem cells are inserted, and patient recovers with new blood production being of healthy red blood cells."
It's very likely HIV could be cured similarly. I believe all the people who have been cured so far are bone marrow transplant recipients in which the marrow had a specific gene or genes.
https://crisprmedicinenews.com/news/clinical-trial-update-po...
This might be of interest
amazing and scary stuff
I think it's too easy to imagine Orwellian scenarios, but I think the real worries are much more subtle than people usually think, and they usually have more to do with how the world already works than with how it could change.