The Genetics Podcast

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

Summary: This week on The Genetics Podcast, Patrick is joined by Melissa Haendel, Director of Translational Informatics and Precision Health and Professor at the University of North Carolina at Chapel Hill, and Phenotypic Lead at Alamya Health. They discuss the limitations of electronic health records for rare disease diagnostics, how patient self-reporting can enhance diagnosis, expanding access to genomic testing in underserved settings, and the challenges and promise of national-scale health data infrastructure. Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Melissa02:05 Melissa’s career path, beginning with finding her first professorship on Craigslist04:24 The fundamentals of ontology and how it can help identify common molecular mechanisms across different rare diseases06:29 Why key rare disease details are missing from electronic health records (EHRs) and how ontologies and AI can help11:33 How patient self-reporting using layperson phenotypic terms was associated with strong diagnostic performance15:27 Why recognizing multi-system patterns is key for diagnosing rare conditions and how tools like pattern-based screening are improving outcomes17:41 How Alamya Health is expanding access to genomic diagnostics by building local lab infrastructure in underserved communities22:03 How Alamya’s single-test, AI-powered approach helps solve complex cases in underserved settings24:18 Rethinking the true cost of delayed diagnosis, from wasted testing to the societal and family burden26:10 What it takes to do national-scale health data research in the U.S. and a vision of real-world data as a public utility33:37 Opening up access to national EHR data for research through health data networks36:15 The gap between real-world data and clinical research and why improving data quality benefits both care and science38:34 A major upcoming milestone in bringing unified rare disease codes into US healthcare with the Mondo ontology41:22 Closing remarks Find out moreTIS Lab (https://tislab.org/), Alamya Health (https://www.alamyahealth.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

Summary: This week on The Genetics Podcast, Patrick is joined by Frank Gentile, Chief Executive Officer of Casma Therapeutics. They discuss the role of autophagy in neurodegenerative diseases, Casma’s work on therapies for Gaucher’s disease and Parkinson’s disease, and the challenges and opportunities in rare disease biotech.Show Notes: 0:00 Intro to The Genetics Podcast00:58 Welcome to Frank 02:00 Origin story for Casma Therapeutics and its therapeutic focus on autophagy04:51 Diseases in which autophagy is dysregulated07:46 The link between GBA1 and Parkinson’s, and why so many neurodegenerative diseases exhibit autophagy defects12:28 Findings from Casma Therapeutics’ preclinical studies and associated mechanisms16:46 Milestones and design of Casma Therapeutics’ upcoming clinical studies20:24 Well-characterized cohorts of GDPD patients from natural history studies21:55 Identifying alternative therapeutic targets involved in autophagy initiation that are mTOR independent24:46 The negative effects of broad inhibition of mTOR25:57 Advantages and disadvantages of using small molecule therapy versus broader gene therapy26:59 Frank’s experience in investment and his approach to risk29:15 Frank’s perspective on the current biotech climate and how investors view rare disease32:16 Extending lead candidate and portfolio strategy to other therapeutic applications 34:15 Partnering opportunities and future potential of the TRPML1 program across neurodegenerative diseases35:50 A potential link between autophagy pathways and longevity37:20 Closing remarksFind out moreCasma Therapeutics (https://www.casmatx.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

Summary: This week on The Genetics Podcast, Patrick is joined by Huma Qamar, Chief Medical Officer at Ocugen. They discuss her journey from arriving in the US with $88 in her pocket to leading gene therapy programs, Ocugen’s breakthrough in retinal disease, and how gene-agnostic therapies could transform treatment for conditions like retinitis pigmentosa.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Huma 01:40 How Huma arrived in the US from Pakistan with $88 and went on to do medical training and research at Yale and Harvard06:47 Huma’s approach to challenges throughout her journey and how networking helped boost her career09:30 Ocugen’s mission to develop therapies for retinal disease and recent successes, including obtaining pediatric breakthrough designation12:10 Technical advantages and disadvantages of Ocugen’s retinal gene therapy 15:18 Insights from Huma’s experience across gene therapy trials versus oncology trials 19:17 Clinical landscape and genetic mutations in retinitis pigmentosa and the advantage of Ocugen’s gene-agnostic and gene modifier platform23:17 Therapy mechanism of reactivating degenerating photoreceptors via master regulators  26:32 Clinical trial design and regulatory considerations29:15 Huma’s vision and hopes for retinal diseases over the next 5-10 years 30:20 Huma’s experience as an interpreter and dedication to supporting immigrants and refugees32:12 Closing remarks and Huma’s message to women and patientsFind out moreOcugen (https://ocugen.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