Jacob Kimmel

But I think we've only very recently actually gotten the tools we need to start addressing transcription factors as first-class targets rather than treating them as like maybe some ancillary third-order thing that's going to happen.

How do you get them in there?

So I think there are many ways one could imagine solving it.

I'll sort of like narrow the scope of the problem to saying, I think delivering nucleic acid is a pretty good first order primitive.

Ultimately, the genome's nucleic acids, the RNAs that come out of it are nucleic acids.

So if you can get nucleic acid into a cell, you can drug pretty much anything in the genome effectively.

So you can reduce this problem to asking, how do I get nucleic acids wherever I want them to any cell type very specifically?

So today, there are two main modalities that people use, both of which have some downsides.

The first one that we've touched on already is lipid nanoparticles.

These are basically fat bubbles.

And by default, they get taken up by tissues which take up fat, like the liver, and they can be used sort of like Trojan horses.

They can release some arbitrary nucleic acid, usually RNA, maybe encoding your favorite genes, in our case, transcription factors.

into the cell types of interest.

You can play with the fats, and you can also tie stuff onto the outside of the fat, like you can attach a part of an antibody, for example, to make it go to different cell types in the body.

And I think the field is making a lot of progress on being able to target various different cell types with lipid nanoparticles.

So even if nothing else worked for the next several decades, I think companies like ours would have more than enough problems to solve with the cells that we can actually target.

Another prominent way people go after this is using viral vectors.

The basic idea being viruses had a lot of evolutionary history and very large population sizes.

They've evolved to get into our cells.

Maybe we can learn something from them, even better Trojan horses.