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Comment by trhway | Hacker News Reader

"Seven days after the girl’s medical team infused trillions of viruses carrying the recipe for the base editor into her spinal fluid, she died of a severe immune reaction linked to the therapy"

questions of a layman - couldn't they initially do a small infusion of the [may be even weakened version of that] viruses to check for the immune reaction? May be such infusion would really serve as a vaccine prepping the immune system for the main infusion later? - though immune system killing the viruses may be nullifying the treatment - then may be when doing such therapy the patient needs to be [somewhat] immunosuppressed similar to transplant situations?

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It could negate the treatment (the vector will be neutralized by the immune system).

that is why after thinking a bit i edited the post adding the opposite track of thought - immunosuppression.

The article mentions that she was given an immunosuppressant (prednisone), but that a more comprehensive course of immunouppressants could have been given.

Acquired immunity is complicated territory. Doing this way could make a future adverse reaction more certain.

But I don't think you're far from the correct procedure. Clinical trials are structured in phases. And AFAIK, safety is the first thing to be determined.

that's why in clinical trials you first do phase 1 human subjects where they are healthy and take small sub-therapeutic doses to test safety/tolerability. once it's established safe in humans they do phase 2 where they test if it works on sick people. Yeah I know this is different with transduction but they could at least test the vector first, maybe they did? Maybe some kind of lentivirus vector

> May be such infusion would really serve as a vaccine prepping the immune system for the main infusion later?

This is correct and exactly the problem. You don't want the immune system to react to the virus, but giving it exposure to the virus will nearly guarantee a reaction. This is why they were checking that the patient didn't have antibodies already.

Here is an article discussing this issue: https://pmc.ncbi.nlm.nih.gov/articles/PMC10673641/

> though immune system killing the viruses may be nullifying the treatment

That's a problem for some types of RNA/DNA vaccines where they use a virus as a vector. You can usually only use a specific kind of virus once per patient.

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