Jacob Kimmel: belief

Transcript context

…We've got 1600 transcription factors in the human genome. Is it worth looking at non-human TFs and seeing what effects they might have, or are they unlikely to be the right search space? 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. In our case, we know that the state we're trying to access 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. 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 Super-SOX. Super-SOX is a particular publication from Sergiy Velychko where they mutated the SOX2 gene and they made more efficient iPSC reprogramming. 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 Oct-4, Sox2, KLF4, and Myc. iPSC reprogramming never happens in nature, so there's no reason to necessarily believe that the natural TFs are optimal. 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. 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. What about the effects of aging? Your skin starts to sag because of the effects of gravity over the course of decades? Is that a cellular process? How would some cellular therapy deal with that?…

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