Unfortunately, AAV is not currently re-dosed, due
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Posted On: 07/05/2022 8:08:07 AM
Unfortunately, AAV is not currently re-dosed, due to immune response to the viral capsid. There are many AAV subtypes .. AAV2, 5, 6, and 9 for instance. Most have tropism for liver. A few for CNS. Not sure which would be able to transfect TCells. Most AAV gene therapy trials have as a requirement no previous infection with that AAV strain that is being used for gene therapy .. no antibodies to it already.
I think perhaps the AAV LRM gene therapy for Tcells HIV cure research project (Sacha NIH grant) may just be a convenient way to ensure adequate LRM availability to prove the proof of concept in an animal model. Not sure it would be feasible in human clinical trial.
Does anyone remember NP saying they were going to try to do an HIV cure in a few humans? In people with HIV who needed a stem cell transplant if I recall correctly. They would ablate the old immune system, infuse the new, and give LRM to try to keep the new cells from being infected. The problem often is that HIV hides out latent in memory T cells, which are very long lived. The concept *did* work in the only 2 or 3 known "sterilizing" cures of HIV, but that was with stem cell donor being CCR5 negative / natural Knockout. Attempts to reproduce that failed, probably because gene editing efficiency of donor cells was not high enough .. too many Tcells with CCR5 still. Why not.combine approaches? Maybe gene editing not required, just dose LRM after donor transplant for a few years ... as originally planned .. according to NP.
I think perhaps the AAV LRM gene therapy for Tcells HIV cure research project (Sacha NIH grant) may just be a convenient way to ensure adequate LRM availability to prove the proof of concept in an animal model. Not sure it would be feasible in human clinical trial.
Does anyone remember NP saying they were going to try to do an HIV cure in a few humans? In people with HIV who needed a stem cell transplant if I recall correctly. They would ablate the old immune system, infuse the new, and give LRM to try to keep the new cells from being infected. The problem often is that HIV hides out latent in memory T cells, which are very long lived. The concept *did* work in the only 2 or 3 known "sterilizing" cures of HIV, but that was with stem cell donor being CCR5 negative / natural Knockout. Attempts to reproduce that failed, probably because gene editing efficiency of donor cells was not high enough .. too many Tcells with CCR5 still. Why not.combine approaches? Maybe gene editing not required, just dose LRM after donor transplant for a few years ... as originally planned .. according to NP.
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