Interesting news. The gene therapy proof of concept story of Victoria Gray was very convincing this week at the third world summit on human gene editing


Expand full comment

Using mRNA is a good balance. mRNA doesn't need to go into the nucleus, it can be translated in the cytoplasm so it is more efficient than DNA gene therapies that need to get into the nucleus. If you're using it for CRISPR gene editing it doesn't matter if the mRNA is only in the cell short-term because the gene edit knockout of the KLKB1 gene, as seen on NTLA-2002 would be permanent.

Don’t really get it- if the mRNA doesn’t get in nucleus, how can it edit a gene? The first and second parts of this paragraph are contradictory.

Expand full comment

Enlightening 🙏🏽

Expand full comment

Specificity is why we use viruses.

Lipid nanoparticles are great for vaccines or liver indications because they infect the first cell they touch. Inject in a muscle and you'll get transgenes expressed in that spot in the muscle (for vaccines). Inject in a blood vessel and you'll get mainly liver cells. targeted. Retinal injections are possible too, and there are some other ways you can physically target the cells of interest, but LNP is simply not specific enough.

In vivo editing isn't something you want to do all over the body either as every cut has a potential for causing cell death or oncogenesis.

So you want something targeting very specific cells in most cases, and that's viruses. Lipid nanoparticles with proteins to specify targets has some proof of concept studies, but right now that's not nearly as close to being made at scale or saving patients as just using AAV.

Biopharma has a lot of inertia and is slow to push innovations into the clinic, but that's because going too fast causes deaths and shuts everything down for decades (specifically to gene therapy the Jesse Gelsinger case). And in the case of lipid nanoparticles because they don't do what we need them to do. Not because we just really really like viruses.

Expand full comment

I might be wrong here, but small typo: "So much money are being burned on viral based systems that have so many drawbacks." I believe that should be is not are in this instance. Also can I get a link to information on alternatives to viral therapies?

Expand full comment