alt Hacker NewsSarepta'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...
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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.
Probably because the HHS secretary is vehemently opposed to lipid nanoparticles.
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.
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.