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Posted On: 07/11/2022 12:25:58 PM
Post# of 148899
This will be in monkeys, like Sacha's other work.
To follow up on previous posts about T-cell AAV gene therapy to produce LRM, I guess most memory T-cells live only for weeks at a time (rejuvenated by new naive T-cells turning into memory T-cells), but there is a subset that appears to never be replaced. We need to transfect the long-lived T-cells if we hope to have a "life-long" gene therapy producing LRM for as long as folks live. It still isn't clear if the "never replaced" memory T-cells live a really long time, or maintain their population by dividing. If by division, the AAV will wash out over time in that population.
Brief review note on T-cell longevity:
https://elifesciences.org/articles/26754
and nice review article summarizing what is known on T-cell development and maintenance in humans:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826622/
Some Chinese groups have already developed AAV for in-vivo T-cell transfection (to create autologous CAR-T cells in situ):
https://pubmed.ncbi.nlm.nih.gov/35223491/
https://pubmed.ncbi.nlm.nih.gov/34162832/
So it should be possible for Sacha et al. to develop AAV to transfect T-cells in monkeys to produce LRM. I still wonder how long the production of LRM will last, as most T-cells don't live very long. That's why they do the experiments!
To follow up on previous posts about T-cell AAV gene therapy to produce LRM, I guess most memory T-cells live only for weeks at a time (rejuvenated by new naive T-cells turning into memory T-cells), but there is a subset that appears to never be replaced. We need to transfect the long-lived T-cells if we hope to have a "life-long" gene therapy producing LRM for as long as folks live. It still isn't clear if the "never replaced" memory T-cells live a really long time, or maintain their population by dividing. If by division, the AAV will wash out over time in that population.
Brief review note on T-cell longevity:
https://elifesciences.org/articles/26754
and nice review article summarizing what is known on T-cell development and maintenance in humans:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826622/
Some Chinese groups have already developed AAV for in-vivo T-cell transfection (to create autologous CAR-T cells in situ):
https://pubmed.ncbi.nlm.nih.gov/35223491/
https://pubmed.ncbi.nlm.nih.gov/34162832/
So it should be possible for Sacha et al. to develop AAV to transfect T-cells in monkeys to produce LRM. I still wonder how long the production of LRM will last, as most T-cells don't live very long. That's why they do the experiments!
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