Virtual Cells, Programmable Biology, and the Quest to Hack Human Aging — Omar Abudayyeh & Jonathan Gootenberg
This week, I sat down with Omar Abudayyeh and Jonathan Gootenberg, the co-PIs who helped pioneer the field of genome engineering, and are now leading one of the most innovative and productive bioengineering labs in the world.Omar and Jonathan met as graduate students in the lab of CRISPR pioneer, Feng Zhang. They have since co-authored more than 30 breakthrough papers that helped transform CRISPR-Cas from a basic research tool into a clinically relevant therapeutic and diagnostic modality. Their work has led to the founding of companies like Sherlock Biosciences, Proof Diagnostics, and Tome Biosciences. Their mission is to make biology programmable, and here’s the progress they have already made towards that goal:* EvolvePro: To compress months of directed evolution into weeks by combining protein language models with experimental iteration* STITCHR: For scarless and efficient DNA insertions ranging from a single base to 12.7 kb* PRECISE: For writing RNA of arbitrary length and sequence into existing pre-mRNAs* Virtual Cell: To model cell states and perturbations to predict or control cellular behavior * Secretome Project: To systematically test human secreted peptides for desirable therapeutic phenotypes, like muscle gain and organ rejuvenation.And in case you’re short on time, here’s a quick teaser:Watch on YouTube; listen on Apple Podcasts or Spotify.GUEST INFORMATION:* AbuGoot Lab * EvolvePro * STITCHR* PRECISE* PASTE* X (Twitter): @omarabudayyeh @jgootCONNECT WITH US:* Website* Substack* YouTube* X (Twitter)* LinkedIn* TikTok Get full access to Frameshifts at frameshifts.bio/subscribe
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Francisco LePort & Martin Borch Jensen: The Biotech Founders Testing 25 Drugs in One Horse | Frameshifts Episode #3
In this week’s episode, I sit down with Francisco LePort and Martin Borch Jensen, the co-founders of Gordian Biotechnology. Gordian is revolutionizing drug discovery by testing where it matters most… directly in living organisms. We discuss their groundbreaking approach of pooled in vivo screening that transforms a single organism into thousands of parallel experiments, and how this could fundamentally change our approach to studying age-related diseases.Francisco and Martin believe that traditional anti-aging drug discovery has been ignoring the biology of aging itself. Instead of testing drugs in mice (equivalent to studying osteoarthritis in 25-year-olds), they are using actual horses that developed arthritis naturally and thus better represent aging as it actually manifests. Their early results suggest we might be on the cusp of a new era where we can finally address the root causes of multiple age-related diseases simultaneously.This episode covers:* Why aging research ignores actual aging biology, and how this kills drug development* How to do the work of 10,000+ animal studies in a single experiment using gene therapy and single-cell sequencing* How Francisco & Martin deliberately “killed their ambition” to go after aging directly* The policy disasters strangling US biotech innovation (and why China’s gaining ground)* How failed clinical trials waste billions in data that never gets analyzedAnd in case you’re short on time, here’s a quick teaser:Watch on YouTube; listen on Apple Podcasts or Spotify.GUEST INFORMATION:* Francisco LePort* Martin Borch Jensen* An Autocrine Signaling Circuit In Hepatic Stellate Cells Underlies Advanced Fibrosis In Nonalcoholic Steatohepatitis* In-Vivo Pooled Screening* Gordion BiotechnologyCONNECT WITH US:* Website* Substack* YouTube* X (Twitter)* LinkedIn* TikTok Get full access to Frameshifts at frameshifts.bio/subscribe
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Ron Weiss: Building Biological Neural Networks to Fight Cancer | Frameshifts Episode #2
In this week's episode, I sit down with Prof. Ron Weiss, the MIT pioneer who helped create the field of synthetic biology. We discussed the emergence of living therapeutics that can think, adapt, and make complex decisions inside the human body. The implications of this stretch from synthetic cells within implantable biosensors that can produce insulin based on real-time glucose sensing to self-amplifying RNAs encoding gene circuits that specifically detect and kill cancer cells.Ron believes the future of medicine lies in treating biological systems as sophisticated analog computers… systems we can learn to program. While this may still seem like a distant future, the first therapeutic fruits of this approach are already on their way to the market. And in case you’re short on time, here’s a quick teaser on the “REACT” ARPA-H project that Ron’s lab is working on:Watch on YouTube; listen on Apple Podcasts or Spotify.GUEST INFORMATION:* Prof. Ron Weiss* Weiss Lab for Synthetic Biology* Programming gene and engineered-cell therapies with synthetic biology* PERSIST platform provides programmable RNA regulation using CRISPR endoRNases* Synthetic neuromorphic computing in living cells* LinkedinCONNECT WITH US:* Website* Substack* YouTube* X (Twitter)* LinkedIn* TikTok Get full access to Frameshifts at frameshifts.bio/subscribe
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Kevin Esvelt: Sculpting Evolution, Engineered Viruses and Safeguarding Biotechnology | Frameshifts Episode #1
“What I wanted to do was harness evolution as effectively as possible.”In this episode, I sit down with pioneering synthetic biologist Kevin Esvelt. Together, we explore how technologies like gene drives and phage-assisted continuous evolution could help tackle humanity’s toughest challenges, from eradicating malaria to protecting global food security. We also dig into the urgent need to safeguard biotechnology against misuse.This is a conversation about the future of science, biosecurity, and society, and how we can harness biology safely to create a healthier, more equitable world.🔔 SUBSCRIBE so you don’t miss our next conversation! GUEST INFORMATION:Prof. Kevin EsveltSculpting Evolution Group at MITThe Original PACE Paper (Nature, 2011)Gene Drives Paper (eLife, 2014)X (Twitter) CONNECT WITH US:WebsiteSubstackYouTubeX (Twitter)LinkedInTikTok Get full access to Frameshifts at frameshifts.bio/subscribe
Join us for a fascinating conversation with Betty Zhang, an Investment Associate at Boson Ventures, who is at the forefront of biotech innovation and investment. In this episode, Betty shares her journey from a passionate science student to a key player in venture capital, where she influences significant advancements in healthcare and biotech.Betty discusses her unique path, which took her from academic research to recognising the pivotal role of strategic investments in transforming scientific breakthroughs into commercial successes. She highlights her involvement in the MedTech Actuator Accelerator and insights into the investment landscape, especially how strategic capital allocation can drive the next generation of medical technologies.Tune in to this insightful episode of Insane Ambition to understand the complex interplay between science, investment, and innovation. Available now on Spotify, Apple Podcasts, and YouTube. #investment #biotech #innovation #venturecapital #science #business #tech #innovation #leadership #technology #podcast #techshow #startups #insaneambition #podcastA big thanks to Melbourne Connect Co-working, the heartbeat of Australia’s leading innovation precinct, for supporting the production of Insane Ambition and for fuelling the creative spirits that bring our stories to life!Use our discount code "AMBITION" to reserve your co-working space now! Get full access to Frameshifts with Benjamin Arya at frameshifts.bio/subscribe
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