I'm guessing they were looking for preferential delivery to certain cell types, and AAVs just happened to have best profile for those. If anything, LNPs might aggregate in the liver even more than AAVs, which can lead to even worse hepatotoxicity if an immune response happens.
Lipid nanoparticle toxicity has long been an industry concern.
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]
This gene therapy involves a gene called dystrophin, which is one of if not the largest gene in the human genome. Sarepta is actually using a version called microdystrophin, which is a truncated version. It still barely fits into AAV.
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.
> 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.
https://medcitynews.com/2025/07/sarepta-gene-therapy-fatalit...