Jacob Kimmel: belief

Transcript context

…Would it have to be a chronic treatment, or could it just be a one-time dose? In principle, it could be one time. I think that would be an overstatement for today. I can talk you through the evidence from the first principles back to the reality of what's the hardest thing we have in hand. Epigenetic reprogramming is basically how the cell types in our bodies right now are able to adopt the identities that they have. The existence proof that those epigenetic reprogramming events can last decades is that my tongue doesn't spontaneously turn into a kidney. These epigenetic marks can persist for decades throughout a human life, or hundreds of years if you want to take the example of a bowhead whale which uses the same mechanism. We also know that with very targeted edits, other groups have done this, folks like Luke Gilbert now at the Arc Institute, who I think of as one of the great unsung scientists of our time, have been able to make a targeted edit in a single locus and then show that you can actually make cells divide 400-plus times over multiple years in an incubator in the lab. Imagine a hothouse where you're just trying as hard as you can to break this mark down, and it can actually persist for many years. Other companies have actually now dosed some editors similar to the ones that Luke developed in his lab in monkeys and shown they last at least a couple of years. In principle, the upper bound here is really long. 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. I don't want to overstate. We do have data that these positive effects can last several weeks after a dose. 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 to get an IV every day, which might not be tractable. 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?…

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