Troubleshooting the Development of New Gene Therapies (by Khanh Ngo Courtney)

This post is in response to: LINK

This post was well-written. I enjoyed it. I agree that AAVs are far more safe than other viral vectors, given there are not replicating concerns.

However, I think further discussion on these points would be great:

Aren’t there still insertional mutagenesis concerns still associated with AAVs?

Aren’t there still issues with increased clearance if the patients have had previous contact with the type of AAVs being used?

Upon the second dose, as second doses may be necessary in some applications, would not the patient’s immune system be more likely to clear the AAVs more quickly?

It would likely require a priori testing to ensure the patient is not going to clear the AAVs more quickly.