Sarepta's drug uses AAV to deliver the payload. I wonder why they chose AAV instead of lipid nanoparticles.
https://medcitynews.com/2025/07/sarepta-gene-therapy-fatalit...
https://medcitynews.com/2025/07/sarepta-gene-therapy-fatalit...
In a profile of Moderna back in 2016, Katalin Karikó (instrumental in the development of mRNA vaccines) mentioned this issue:
“I would say that mRNA is better suited for diseases where treatment for short duration is sufficiently curative, so the toxicities caused by delivery materials are less likely to occur” [1]
[1] https://www.statnews.com/2016/09/13/moderna-therapeutics-bio...
Reasons to use AAV: they're going for sustained production of the therapeutic gene, and AAVs are better at doing that than LNPs. LNPs were used in the mRNA COVID vaccine, because they're great at transient production.
To get stable production from an LNP you'd likely have to integrate into the genome, which risks cancer from disrupting oncogenes. You'd also need to package the therapeutic gene with a mechanism of integrating into the genome, like recombinase.
https://www.axios.com/2025/04/18/rfk-jrs-potential-future-ta...
https://kffhealthnews.org/news/article/nih-grants-mrna-vacci...
> National Institutes of Health officials have urged scientists to remove all references to mRNA vaccine technology from their grant applications, two researchers said, in a move that signaled the agency might abandon a promising field of medical research.