The Genetics Podcast

This week on The Genetics Podcast, Patrick is joined by Samuli Ripatti, Director of the Institute for Molecular Medicine Finland (FIMM), Vice Director at HiLIFE, and Professor of Biometry at the University of Helsinki. They discuss Samuli’s research on lipid and cardiovascular genetics, how polygenic risk scores are moving into clinical care, and the power of the FinnGen biobank. Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Samuli01:48 Samuli’s path from statistics to genetics at the beginning of a new era03:09 Remembering Leena Peltonen and the Human Genetics Summer School05:46 Samuli’s research in lipid and cardiovascular genetics and the power of collaboration09:14 Integrating polygenic risk scores into cardiovascular and breast cancer care14:52 Using medication history in FinnGen to uncover cardiometabolic genetics and predict treatment patterns18:50 The future of polygenic risk scores in predicting prognosis and guiding treatment21:21 The confounding effect of treatment in genetic studies23:14 Overview of FinnGen and its impact on genetics and drug discovery27:04 The next 5 years in proteomics and molecular profiling to move beyond associations29:56 Using polygenic risk scores in clinical trials31:41 Future directions, from refining phenotypes in large biobanks to piloting clinical applications of polygenic risk scores34:04 Scaling population biobanks versus deep phenotyping and why the future requires both35:29 Closing remarksFind out moreGenetic predictors of lifelong medication-use patterns in cardiometabolic diseases (https://www.nature.com/articles/s41591-022-02122-5)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Jonathan Marchini, Head of Statistical Genetics and Machine Learning at the Regeneron Genetics Center. They discuss Jonathan’s pioneering role in developing computational methods from the HapMap era through to today, how those innovations underpin large-scale imputation and analysis, and why exomes with imputation remain more powerful than whole genomes for discovery at Regeneron.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Jonathan01:47 Jonathan’s career path from teaching in rural Tanzania to genomics research at Oxford04:43 Lessons from the HapMap era and the birth of imputation08:30 Ongoing challenges with data sharing and usable tools 10:30 Handling massive genetic datasets at Regeneron and developing new computational methods to scale15:26 Key discoveries from the million-exome paper18:04 Pushing computational limits in meta-analysis 19:50 Polygenic risk scores in the clinic and their role in trial design23:38 Why Regeneron prioritizes exomes with imputation over whole genomes and what that means for discovery27:58 Where AI truly adds value in genomics and where simpler models still win32:27 Interpreting rare variants, the promise of protein models, and why better phenotyping is key35:31 Closing remarks and opportunities at RegeneronFind out moreRegeneron Genetics Center (https://www.regeneron.com/science/genetics-center)Million exome paper (https://www.nature.com/articles/s41586-024-07556-0)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Max Bronstein, CEO of Aviva Strategies. They discuss the shifting regulatory and political landscape shaping biotech, the realities of today’s drug development process, and why new incentives and flexible trial pathways are critical to advancing rare and ultra-rare disease therapies.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Max01:51 Regulatory shifts and FDA challenges under the new administration05:40 Overview of the regulatory process for therapeutic development and the push for patient-centered trials11:26 Challenges in drug development from regulatory gaps to shifting FDA priorities15:45 Unprecedented government turnover and its impact on biotech industry stability18:32 Status and significance of the pediatric priority review voucher program for rare and ultra-rare disease development22:02 How Congress uses “must-pass bills” to advance or block health policies25:17 Max’s role in creating Advanced Research Projects Agency for Health (ARPA-H) to drive high-risk innovation 30:02 How ARPA-H is funded 31:21 Adapting science policy to politics33:35 Breakthroughs in rare disease therapies and the policy frameworks needed to ensure access37:15 Lessons from the Orphan Drug Act and why new incentives are needed to make ultra-rare disease drug development viable39:23 The push for flexible rare disease trial pathways and the disconnect between FDA rhetoric and practice43:26 Closing remarks and a call to connect for patient organizations and rare disease parentsFind out moreAviva Strategies (https://www.avivastrategies.com/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Richard Wilson, Senior Vice President, Primary Focus Lead of Genetic Regulation at Astellas. They discuss where the gene therapy field stands today, diving into successes, persistent barriers, regulatory considerations, manufacturing strategies, and other reflections on important approaches to precision medicine drug development.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Richard01:33 Current wins and challenges in gene therapy 07:13 The need for more open non-competitive data sharing and a clearer pathway towards reimbursement and incentivization11:15 Building post-approval systems into the genomic medicine lifecycle14:47 Rethinking evidence standards in rare disease trials, and the global push for regulatory and reimbursement alignment20:28 Genetic medicine breakthroughs in central nervous system diseases22:25 The challenges of starting clinical development with an end in mind24:34 The need for careful analysis around endpoints, vector design, and delivery approaches29:33 Navigating regulatory hurdles when making mid-program changes to vectors or payloads31:16 Strategies for enhancing scalability and quality of gene therapy manufacturing 36:05 Exploring other delivery methods beyond AAV39:32 Getting ready for the Timmerman Traverse and raising nearly $1M for Life Science Cares43:48 A call to refocus on patients, partnership, and purpose in uncertain times45:55 Closing remarks Find out moreAstellas (https://www.astellas.com/)Timmerman Traverse fundraising for Life Science Cares (https://timmermantraverse.blackbaud-sites.com/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, we celebrate our 200th episode with a look back at some of the earliest episodes, particularly ones that foresaw major trends or went on to spark real-world impact. These include Eric Topol’s early predictions about AI in healthcare, Laurence Reid’s vision for gene therapy in hearing loss, Sir Rory Collins on the potential impact of the UK Biobank, Daphne Koller on uniting biology and machine learning, and Vineeta Agarwala on harnessing large datasets for drug discovery. Patrick adds updates and reflections on how these bold ideas have shaped the genomics and biotech landscape.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Overview of episode content and guests featured01:47 Eric Topol predicts the role of AI in healthcare in 201905:58 Patrick’s reflections on AI’s progress today and future potential06:57 Laurence Reid outlines Decibel Therapeutics’ gene therapy plans for otoferlin-related hearing loss 10:58 Patrick’s updates on Decibel’s success and acquisition by Regeneron 11:44 Sir Rory Collins on the creation and vision of the UK Biobank18:20 Patrick on the lasting impact of open science and the UK Biobank19:10 Daphne Koller on building insitro to fuse biology and machine learning 24:30 Patrick on the future of large-language models in biology25:55 Vineeta Agarwala on investing in large datasets for drug discovery32:24 Patrick on applying multi-omic data to rare disease research32:52 Closing remarksFind out moreThe Genetics Podcast is now on Instagram! Follow us for clips from recent episodes and release announcements (https://www.instagram.com/thegeneticspodcast/).Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Xin Jin, Associate Professor in the Department of Neuroscience at The Scripps Research Institute. They discuss how in vivo Perturb-seq enables scalable and high-resolution modeling of neurogenetic disorders like autism, how introducing mutations directly into living mouse brains reveals cell-type vulnerabilities and convergent pathways, and why this approach could transform therapeutic development by identifying shared mechanisms across diverse genetic mutations.Show Notes: 0:00 Intro to The Genetics Podcast00:58 Welcome to Xin 01:52 Overview of in vivo Perturb-seq05:10 Identifying de novo variants in autism spectrum disorder09:00 Using perturbations to map how autism-linked mutations affect specific brain cell types13:04 Applying Perturb-seq to other brain diseases14:30 In vivo versus in vitro models and extending genetic screening approaches beyond the brain18:44 Using in vivo models to trace variant effects, rank gene drivers, and uncover therapeutic pathways22:35 Conservation of genes between mouse and human in the context of neurodevelopmental disease modeling 24:21 Impact of genetic discoveries on drug development by convergence onto common pathways 27:22 Xin’s early interest in science through her grandfather’s work in plant taxonomy and botany29:48 Xin’s path from China to MIT and how early research shaped her scientific mindset31:58 Reflections on AI’s rapid progress and limits in biology, and the need for new models 37:21 Closing remarksFind out moreJin lab (https://www.jin.scripps.edu/)In vivo Perturb-seq explainer video (https://vimeo.com/549737357)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Benny Sorensen, CEO of Hemab Therapeutics, leads a groundbreaking company focused on innovative blood clotting therapies, prioritizing patient voices. He shares how persistence and an 'unreasonable' approach catalyzed their first drug development program. The discussion highlights advancements in treating conditions like Glanzmann's thrombocytopenia, the importance of gender considerations in healthcare, and lessons learned from integrating patient experiences. Benny reflects on the balance between leadership and fatherhood, inspiring a vision for empathetic, effective therapies.

Summary: This week on The Genetics Podcast, Patrick is joined by Heiko Runz, medical geneticist and VP of Neuroscience at insitro. They discuss Heiko’s path into therapeutic genetics, how collaboration and data integration across biobanks led to his discovery of a protective variant for age-related macular degeneration, and the role of cell-based models in drug discovery.Show Notes: 0:00 Intro to The Genetics Podcast00:58 Welcome to Heiko01:41 Heiko’s career path and how he became interested in medical genetics and therapeutic development05:49 Connecting the dots across biobanks for genetic discovery08:23 Heiko’s discovery of a potential gene target for age-related macular degeneration15:29 The challenge of biobank recontact and why it’s essential for follow-up studies18:57 The opportunity for smaller companies to follow up on large-scale genomic discoveries23:00 Advances in cell-based models for neuroscience drug discovery24:40 Heiko’s role in the development of tofersen for SOD1 ALS  28:50 Targeting TDP-43 in ALS through large-scale cell-based phenotyping and drug discovery30:36 Using cell-based phenotypes to functionally test disease mechanisms and validate variants33:58 The potential of AI for refining phenotypes and generating drug hypotheses36:47 Heiko’s advice to early career professionals interested in the field of genetics and drug discovery38:26 Closing remarks Find out moreinsitro (https://www.insitro.com), study on CFHR5 (https://www.nature.com/articles/s41467-025-61193-3)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Molly He, CEO and co-founder of Element Biosciences. They discuss the current landscape of sequencing technologies, Element’s innovative sequencing platform, and the potential of using in-sample multiomic profiling across different stages of drug discovery. Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Molly01:42 Persistent barriers in precision medicine04:54 Limitations of multiomics technologies and the unique advantage of Element’s approach07:33 How Element started by inventing an ambitious sequencing instrument11:33 Overview of the chemistry behind Element’s sequencing technology14:41 Sequencing workflow of Element’s technology and technical advantages18:24 Sequencing inside cells and drug discovery insights from a study on tyrosine kinase inhibitor (TKI) resistance pathways25:57 Sequencing for CRISPR perturbation and direct genotype–phenotype linkage in the same cell27:33 Whole-transcriptome in situ sequencing and applications in patient samples29:19 Simplifying single-cell transcriptomics with direct in-sample sequencing30:31 Applying the single-cell spatial technology to different steps of the drug discovery process36:43 Competition in the sequencing industry and recent news about Illumina filing a patent infringement case against Element38:43 Lessons from building Element over eight years40:32 Insight into maintaining a cohesive culture as Element has multiplied in size and across countries42:06 The importance of input data quality for AI applications and excitement about the possibility of predicting biology45:40 Closing remarksFind out moreElement Biosciences (https://www.elementbiosciences.com/)Pre-print (https://www.biorxiv.org/content/10.1101/2025.05.06.652479v1)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

Summary: This week on The Genetics Podcast, Patrick is joined by David Bumcrot, Chief Scientific Officer of CAMP4 Therapeutics. They discuss David’s involvement in the development of the breakthrough technologies in RNA interference and CRISPR, how CAMP4 is pioneering the use of regulatory RNAs to treat haploinsufficient diseases, and the complexities of gene regulation. Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to David 01:57 David’s experiences at companies that developed RNA interference (RNAi) and CRISPR technologies04:05 Lessons from translating RNAi to the bedside 05:58 The scalable chemistry of RNA versus the complexity of gene editing07:48 Insight into the lack of rapid scalability and growth in gene therapy companies09:19 How CAMP4 is using regulatory RNAs to boost gene expression in haploinsufficient diseases13:01 Mapping and predicting the impact of specific regulatory RNAs on the expression of target genes15:05 Why regulatory RNAs open up new target space without needing new drug modalities16:27 How CAMP4 prioritizes certain diseases based on delivery feasibility and genetic evidence18:31 Understanding expression thresholds in haploinsufficiency and building confidence in therapeutic targets 20:29 Comparing different approaches for increasing gene expression22:39 Other therapeutic areas of focus for CAMP4, including urea cycle disorders and central nervous system (CNS) disorders25:47 Lessons from early clinical development and engaging regulators on novel targets27:47 Building high-resolution regulatory RNA maps beyond what public datasets can provide31:04 Considerations around the treatment window for SYNGAP132:40 The value of collaborative frameworks for rapid therapy development 35:20 Rethinking early safety assessment and global regulatory strategies for RNA therapies38:37 The importance of basic science, staying optimistic, and continuing to invest in biotech innovation40:18 Closing remarksFind out moreCAMP4 Therapeutics (https://www.camp4tx.com)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link