![]() Was that the starting point for Scribe Therapeutics? We envisioned that genetic medicine will by and large be in vivo, and in the ideal world we would be able to get to the cells that matter the most for each specific disease. I did this work jointly between David Savage and Jennifer Doudna, and when I graduated in 2017, we sat down for a serious discussion about what we were doing, what was needed at the time, and what was needed to enable the next 20 years of genetic medicine. This allowed us to create Cas9 switches that could turn on or off in response to small molecules, or even sense the presence of other proteins in the cell. We developed topological mutagenesis techniques for many different outcomes, including domain insertions and deletions, and circular permutation to reorganise the ordering of the amino acid sequence. ![]() Together with the lab, I set out on a series of engineering journeys for Cas9 to understand this molecule better and create derivatives with enhanced functions. So you now had the CRISPR-Cas9 technology at your disposal starting out as a PhD student. I realised that this was the perfect time for me to start graduate school and I joined Jennifer’s lab to conduct my PhD, under the co-supervision of David Savage, who is also a co-founder of Scribe. And then CRISPR-Cas9 emerged and suddenly I was free to target anything I wanted. Yes! We had been working 80-hour weeks for 2 years trying to develop a code that could figure out how to bind zinc finger targets so that we could target any location in the genome. And then Jennifer Doudna and Emmanuelle Charpentier published that seminal paper on CRISPR-Cas9 in 2012, right? For two years I built huge unbiased libraries of zinc finger nucleases. I knew that trying to build the necessary technical skills would be crucial, so rather than going straight into graduate school, I joined Marcus Noyes’ lab at Princeton University that focused on engineering zinc finger nucleases. This really motivated my transition from wanting to be a doctor or an MD with a PhD, to wanting to build those missing tools. It still isn't today, and that's not a problem with medicine, but more a problem with not having the tools to do so. But in shadowing doctors in rural Maine, I quickly realised that most of medicine wasn't focused on treating the underlying causes of disease. I actually started out studying to be a medical doctor. Can you tell me how you ended up working in this area? You are one of the founders, along with Brett Staahl, David Savage, and Jennifer Doudna herself. Scribe Therapeutics spun out of Jennifer Doudna’s lab at UC Berkeley in 2018.
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