Jacob Kimmel

You could potentially have one dose and it lasts a very long time, potentially decades, as long as it took you to age the first time maybe.

We don't have data like that today, so we don't want to overstate.

We do have data that these positive effects can last several weeks after a dose.

And so you could imagine, even without many leaps of faith up toward this upper bound limit of what's possible, just from the data we have in hand now, that you could get doses every month, every few months, and actually have really dramatic benefits that persist over time, rather than needing, for instance, to get an IV every day, which might not be tractable.

I think it's less likely.

I think you have a prior that evolution has given you a reasonable basis set for navigating the states that human cells might want to occupy.

And in our case, we know that the state we're trying to access exists.

is encoded by some combination of these TFs.

It does arise in development, obviously.

We're trying to make an old cell look young, not look like some Frankenstein cell that's never been seen before.

That said, we don't have any guarantees that the way aging progresses is by following the same basis set of these transcription factor programs in the genome that are encoded during development.

So I don't think it's unreasonable to ask

Would your eventual ideal reprogramming medicine necessarily be a composition of the natural TFs or would it include something like TFs from other organisms as you posit or even entirely synthetic transcription factors as well?

Things like SuperSox.

SuperSox is a particular publication from Sergei – I mispronounced his last name – Vilachenko.

where they mutated the SOX2 gene and they made more efficient iPSC reprogramming.

So they could take somatic cells and turn them into pluripotent stem cells more effectively than you could with just the canonical Yamanaka factors, which are OCT4, SOX2, KLF4, and MYC.

IPSC reprogramming never happens in nature, so there's no reason to necessarily believe that the natural TFs are optimal.

And so even really simple optimizations, like just mutagenizing one of the four Yamanaka factors we already know about or swapping some domains between a few TFs seem to improve things dramatically.

So I think that's a pretty good signal that actually there's a lot of gradient to climb here and that potentially for us, the end state products we're developing in 2100 are more like synthetic genes that have never existed rather than just compositions of the natural set.