Replies to post #185261 on Biotech Values

[poorgradstudent]

CLDN:

Intracoronary delivery resulted in 2.6- to 28-fold higher transgene protein expression in the heart 3 weeks after AAV injection compared to intravenous delivery depending on AAV serotype.

Yes. What the authors are writing is very correct for rats, as they indicate. In my experience, IV and intracoronary delivery for cardiotropic AAV serotypes are both very effective in rats and mice.

However, when you go to larger animals, the degree of cardiotropism from intracoronary injection (even with recirculation!) is significantly reduced to the point of being ineffective. Perhaps it's due to different patterns / availability of the carbohydrates that the AAV uses to recognize its points of attachment, in addition to much larger dosing requirements. CLDN's own data showed that their intracoronary injection did not increase protein expression in a pig model.

I wish this challenge posed by AAVs were different as it would have made the experiments much easier.