Advertise on podcast: The Genetics Podcast

This week on The Genetics Podcast, Patrick is joined by Lindsey Wahlstrom, Co-Founder and Chief Momatologist of Rona’s FUN LAB, Jimi Olaghere, sickle cell disease patient advocate and early CRISPR gene therapy trial participant, and Rachel Smith, Vice President and Head of Rare and Genetic Diseases at Parexel. They discuss the realities of developing and delivering advanced therapies in rare disease, how funding models, regulation, and trial design shape access and outcomes, and why embedding patient experience early is critical to building therapies that are not only effective but scalable, accessible, and meaningful for patients and families. Show Notes:  0:00 Intro to The Genetics Podcast 01:00 Welcome to guests and what Rare Disease Day means to them 08:09 Balancing hope with funding, pricing, and access in advanced therapies 11:48 Why patient access must be built into drug development from day one 14:20 Patient engagement, community readiness, and the realities of trial participation 17:49 Why early patient input is still inconsistent and often treated as a checkbox 23:20 Designing trials around what actually matters to patients and families 26:53 Navigating regulators, payers, and trial design constraints in rare disease therapies 36:02 Redefining success in gene therapy around access, scalability, and real patient benefit 43:27 Closing remarks

This week on The Genetics Podcast, Patrick is joined by Dr. Suzanne Schindler, Associate Professor of Neurology at Washington University in St. Louis. They discuss how blood-based biomarkers like p-tau217 are transforming our ability to detect and stage Alzheimer’s disease, how “clock models” can estimate when symptoms may begin, and how combining biomarkers with clinical phenotyping could improve trial design, prognosis, and patient care. Show Notes 0:00 Intro to The Genetics Podcast 00:59 Welcome to Suzanne 01:35 Neurobiology of Alzheimer’s disease and how it differs from dementia 06:22 Presymptomatic changes to phosphorylated tau (p-tau) in the brain 07:36 The role of the APOE gene in Alzheimer’s 09:07 Differences in neuropathology in women vs men with Alzheimer’s 10:19 Rare cases where amyloid and tau pathology do not align in Alzheimer’s 12:37 Using plasma p-tau217 trajectories to estimate when Alzheimer’s symptoms may begin 17:30 Using p-tau217 to select clinical trial participants and predict progression timelines 20:59 Overview of therapeutic strategies in Alzheimer’s disease 24:24 Why APOE effects may not appear in p-tau217 measurements 26:30 Combining biomarkers and clinical phenotyping to understand disease progression in Alzheimer’s 30:08 Early-onset vs late-onset Alzheimer’s and differences in clinical presentation 31:45 Expanding beyond p-tau217 to proteomics and multimodal biomarkers for predicting symptoms 33:52 MTBR-tau243 as a more specific marker of tau pathology and Alzheimer’s symptoms 37:31 Expanding biomarkers beyond Alzheimer’s and bringing blood tests into clinical practice 38:49 Closing remarks Find out more: Phosphorylated tau217 study MTBR-tau243 study

This week on The Genetics Podcast, Patrick is joined by Derek Ansel, Global Vice President and Therapeutic Strategy Lead for Rare Disease and Oncology at Worldwide Clinical Trials. They discuss how contract research organizations design and run rare disease trials, the challenges of selecting endpoints and patient populations, and how emerging approaches like n-of-1 therapies, regulatory flexibility, and AI are reshaping clinical development.Show Notes 0:00 Intro to The Genetics Podcast 00:59 Welcome to Derek 01:38 The role of Contract Research Organizations (CROs) in clinical development 02:41 Why endpoints are the hardest problem in rare disease trial design 05:24 How Derek’s team chooses and operationalizes endpoints in rare disease trials 08:14 Balancing patient selection, signal detection, and trial feasibility in rare disease 11:55 How the FDA’s new guidance for personalized therapies could accelerate rare disease drug development 14:20 Patient engagement, genetic counseling, and decision-making in genetic trials 19:30 Patient and clinician dynamics in genetic subtypes of common disease 23:05 What needs to change to make n-of-1 therapies scalable and accessible 26:12 Where AI is delivering real impact in clinical trials today and where it is heading 31:24 Operational bottlenecks, risk tolerance, and the limits of AI adoption in clinical trials 34:55 Derek’s path from early clinical research roles to genetic counseling and rare disease drug development 38:51 Key areas driving progress in rare disease over the next five years 41:42 Closing remarks Please consider rating and reviewing us on your chosen podcast listening platform! 

This week on The Genetics Podcast, Patrick is joined by Dr. Tim Jobson, consultant physician and gastroenterologist at Somerset NHS Foundation Trust and Medical Director of Predictive Health Intelligence (PHI). They discuss the rising burden of metabolic liver disease and how routine clinical data can be used to detect disease earlier and prevent late-stage presentation. They also discuss the LiveWell study, a collaboration between Sano Genetics and PHI, and what it reveals about layering genetics and other data types to improve risk stratification and clinical trial recruitment.  Show Notes 0:00 Intro to The Genetics Podcast 00:59 Welcome to Tim 01:50 The rise of metabolic liver disease and worsening mortality trends 04:35 Motivation and goals behind the Somerset Liver Improvement Program to address late diagnosis 09:13 Where genetics is already used in liver disease and where it’s still emerging 13:17 Current tools for staging liver disease and the challenge of predicting progression at scale 18:48 How the LiveWell study could improve risk prediction and reshape trial recruitment in liver disease 23:58 Applying longitudinal risk detection beyond liver disease to cardiometabolic and other chronic conditions 26:35 Using subtle changes in routine blood tests to identify cancer risk earlier 28:09 Using existing health data to drive earlier intervention and maximize patient impact 30:05 Expanding beyond liver disease, scaling early detection, and advancing precision medicine 32:18 Closing remarks Please consider rating and reviewing us on your chosen podcast listening platform! 

This week on The Genetics Podcast, Patrick is joined by Dr. Glenn Cohen, Professor at Harvard Law School. They discuss the evolving legal and ethical landscape of reproductive genetics, why regulation in areas like embryo selection remains limited, and questions arising around the use of AI in healthcare. Show Notes:  0:00 Intro to The Genetics Podcast 00:59 Welcome to Glenn 01:35 An overview of the courses Glenn teaches at Harvard Law School 02:29 Glenn’s areas of expertise across biomedical ethics 03:20 Ethical considerations around reproductive medicine and polygenic risk scores 10:37 Regulatory uncertainty and limited oversight in reproductive genetics 13:18 Liability, regulation, and real-world implementation challenges for AI in healthcare 14:52 Risk–benefit framework for evaluating AI use in clinical settings 17:19 Glenn’s experience contributing to landmark Supreme Court cases in biotechnology and health law 20:09 Glenn’s perspective on mitochondrial replacement and its regulatory divide between the UK and US 22:20 Closing remarks Please consider rating and reviewing us on your chosen podcast listening platform!

This week on The Genetics Podcast, Patrick is joined by Dr. Andrea Ganna, Associate Professor at the Institute for Molecular Medicine Finland (FIMM). They discuss the promise and limits of polygenic risk scores for disease prediction and clinical trials, how large-scale electronic health records and AI models could transform medical research and healthcare planning, what Finland’s national health data infrastructure enables for population-scale studies, and how genetics can be used to strengthen trial emulation in observational data. Show Notes:  0:00 Intro to The Genetics Podcast 00:59 Welcome to Andrea 01:51 Andrea’s research focuses, including polygenic scores in biobanks and AI applications  03:02 Complementarity between polygenic scores and electronic health record–derived risk signals across biobanks 04:47 Using polygenic risk scores for prognostic versus predictive enrichment in clinical trials 10:28 Limitations and opportunities of using AI models on large-scale electronic health records 15:47 Legal, data infrastructure, and privacy barriers to building AI models on health records 18:04 Choosing model architectures for healthcare AI  19:47 Using AI and multi-omics data to integrate biological knowledge and the challenge of learning causality 21:43 How removing genetic effects from proteins improves disease prediction and highlights the role of environment 24:42 Finland’s health data ecosystem and national biobanks 28:11 Using genetics to improve trial emulation in biobank data and observational studies 33:42 Closing remarks Find out more: Trial emulation study Polygenic scores study Please consider rating and reviewing us on your chosen podcast listening platform! 

This week on The Genetics Podcast, Patrick is joined by Dr. Anna Lindstrand, Professor and Consultant in Clinical Genetics and Genomics at the Karolinska Institute. They discuss how Sweden has scaled whole genome sequencing as a first-line test for rare disease, what long-read sequencing adds to clinical diagnostics, how national genomic infrastructure can accelerate translation into precision medicine, and where prevention and adult genomic screening may fit into the future of healthcare. Show Notes 0:00 Intro to The Genetics Podcast 00:59 Welcome to Anna 01:34 Choosing between whole genome, exome, panels, and long-read sequencing in clinical practice 04:05 Evaluating long-read sequencing in the clinic  06:37 What long-read sequencing adds to diagnostic yield 09:15 The role of RNA sequencing, proteomics, and methylation profiling as complementary tools in clinical genomics 13:07 Building a coordinated national infrastructure for clinical genomics and rare disease research in Sweden 18:20 The shift toward precision therapeutics and new standards for clinical actionability 23:18 Using national genomic data and registries to make Sweden trial-ready for precision therapies 27:01 Moving beyond monogenic models to capture polygenic and borderline signals in clinical genomics 30:44 Genomics for prevention including adult screening and pharmacogenomics 36:23 Anna’s research priorities for the next phase of genomic medicine and structural variant discovery 38:32 Closing remarks Find out more: Long-read sequencing study Moving beyond monogenic disease paper Please consider rating and reviewing us on your chosen podcast listening platform!

This week on The Genetics Podcast, Patrick is joined by Dr. Matthew Goldstein, CEO of jscreen. They discuss his journey from physician-scientist and biotech founder to leading a national nonprofit focused on preventive genetic screening, how a personal tragedy reshaped his mission around carrier screening and access, and what it will take to close the gap between the promise of genomics and its real-world implementation in healthcare. Show Notes:  0:00 Intro to The Genetics Podcast 00:58 Welcome to Matthew 01:41 Matthew’s path from an MD-PhD to founding a personalized cancer vaccine biotech 09:06 From personal tragedy to leading jscreen to expand access to reproductive carrier screening  17:11 Purpose, grief, and how Matthew has led jscreen in honor of his daughter 20:38 The implementation gap between genomic potential and real-world preventive screening  23:33 Nonprofit models, reimbursement barriers, and building sustainable access to preventive genetic screening 28:27 Lessons from the Jewish community’s experience with Tay-Sachs and gaps in understanding 33:05 Preconception carrier screening and the role of community in preventive health 38:04 Closing remarks Find out more: jscreen

This week on The Genetics Podcast, Patrick is joined by Dr. Ryan Dhindsa, Assistant Professor at the Baylor College of Medicine and PI at Texas Children’s Hospital, and Dr. Caleb Lareau, PI at Memorial Sloan Kettering Cancer Center and Assistant Professor of Computational Biology and Medicine at Weill Cornell Medicine. They discuss how a Twitter DM sparked a multi-year collaboration to extract Epstein–Barr virus signals from large-scale human genomic datasets, how measuring viral persistence in UK Biobank data reveals insights into autoimmune disease risk and host genetic control, and what this work means for understanding the long-term impact of chronic viral infections on human health. Show Notes:  0:00 Intro to The Genetics Podcast 00:59 Welcome to Ryan and Caleb 01:58 How a Twitter DM led to a long-term collaboration 03:10 Rescuing Epstein–Barr virus (EBV) sequences from human whole genome data  04:45 Quantifying EBV persistence in UK Biobank, validating the signal, and uncovering links to autoimmune disease 12:00 Computational virology, chronic viral effects on human disease, and extending the approach to the broader human virome 16:59 Design considerations for population genomics programs to better capture chronic viral effects on human disease 21:30 Genetic, viral strain, and environmental factors that shape EBV persistence and immune control 26:09 Future directions for EBV research and expanding beyond European ancestry cohorts 29:46 Focus areas of Ryan’s research including rare variant genetics, neurological disease mechanisms, and pediatric population genomics 33:49 Focus areas of Caleb’s research including the human virome and expanding sequencing technologies to detect uncharacterized nucleic acids 37:03 Where genomic “dark matter” may underlie unexplained cancer and severe disease 38:46 Gaps in non-coding variant interpretation and incomplete penetrance in unsolved genetic disease 42:01 Closing remarks Find out more: Ryan’s research group Caleb’s research group

This week on The Genetics Podcast, Patrick is joined by Dr. Nicky Whiffin, Associate Professor and Wellcome Career Development Fellow at the Big Data Institute, University of Oxford. They discuss the discovery of a new neurodevelopmental syndrome caused by mutations in the small nuclear RNA gene RNU4-2, what this reveals about the non-coding genome and the spliceosome, and how large-scale genome sequencing is reshaping diagnosis, variant interpretation, and the future of genetic medicine. Show Notes:  0:00 Intro to The Genetics Podcast 00:59 Welcome to Nicky 02:09 Overview of the non-coding genome and its functional elements 03:59 How small nuclear RNAs drive splicing and exon recognition 04:54 Overview of the major and minor spliceosomes and the role of small nuclear RNAs in intron removal 06:34 Discovery of recurrent de novo RNU4-2 mutations in developmental disorders through large-scale genomics data 12:18 Growth of patient advocacy groups and global networks following the discovery of ReNU syndrome 14:43 Potential for antisense oligonucleotide therapies for ReNU syndrome 16:06 Clinical endpoints, treatment timing, and biomarker development for ReNU 18:32 Impact of RNU4-2 discovery on exome design, genome sequencing adoption, and targeted testing strategies 19:52 Distinct dominant, recessive, and retinal phenotypes arising from variants within RNU4-2 22:15 Open questions on mutation rates and selection in spliceosomal small nuclear RNAs 25:25  Limits of non-coding variant discovery and the unresolved genetic burden in developmental disorders 29:52 Therapeutic upregulation strategies targeting untranslated regions in haploinsufficiency  33:40 The MRC Centre of Research Excellence in Therapeutic Genomics’ approach to scalable genetic medicines 35:54 Long-term prospects and delivery challenges for gene editing approaches  36:56 Newborn genome screening, actionability debates, and implications for rare disease diagnosis 40:25 Population genomics insights from unascertained newborn genome sequencing cohorts 42:04 Closing remarks Find out more: ReNU discovery paper

This week on The Genetics Podcast, Patrick is joined by Dr. David Dismuke, Chief Technical Officer at Forge Biologics, and Dr. Steven Gray, Professor at UT Southwestern Medical Center. They discuss the evolution of AAV gene therapy from academic labs to industrial-scale manufacturing, how vector design and capsid engineering are improving CNS delivery, and what manufacturing innovation and next-generation delivery technologies mean for safety, cost, and the future of gene therapy. Show Notes:  0:00 Intro to The Genetics Podcast 00:59 Welcome to David and Steven 01:47 David and Steven’s overlapping academic paths and long-term collaboration 03:39 Steven’s research on AAV engineering for central nervous system (CNS) gene therapy 04:50 Forge Biologics’ platform approach to scalable AAV manufacturing 06:28 How AAV vectors are manufactured 08:24 How CNS AAV vectors are designed, tested, and refined across programs 10:58 How manufacturing quality and trial outcomes can shape AAV development decisions 15:13 Factors that impact the ratio of full versus empty AAV capsids 17:21 Manufacturing scale, capsid efficiency, and the future cost curve of AAV gene therapy 24:19 Scaling AAV manufacturing for common diseases and the shift toward industrialized production models 27:07 Engineered AAV capsids for CNS delivery and the tradeoffs between innovation and platform stability 30:31 Next-generation AAV delivery and gene editing technologies 34:41 Lessons from Jude Samulski on translating AAV science into real-world therapies 37:21 Closing remarks Find out more: Forge Biologics

This week on The Genetics Podcast, Patrick is joined by Daniel Chung, Chief Medical Officer of Beacon Therapeutics. They discuss lessons from developing the first ocular gene therapy (Luxturna), the complexities of designing and executing pivotal trials in inherited retinal disease, and how endpoint selection, delivery, and immunogenicity shape clinical and commercial success. Show Notes:  0:00 Intro to The Genetics Podcast 00:59 Welcome to Daniel 01:57 Daniel’s firsthand experience with the development and approval of Luxturna for inherited retinal dystrophy 06:13 Factors contributing to delays in approval for gene therapies in recent years  08:13 Overview of ocular diseases and their suitability for gene therapy 11:40 Why Daniel joined Beacon Therapeutics and current priorities for the lead program 13:22 Key challenges in designing and executing a pivotal gene therapy trial for X-linked retinitis pigmentosa (XLRP) 15:49 Lessons from prior inherited retinal disease trials and selecting the right clinical endpoints 21:03 Expanding beyond the lead program into earlier patients and additional ocular indications 23:43 AAV packaging constraints and managing immunogenicity in ocular gene therapy 26:29 Lessons from academia–industry collaboration in developing gene therapies 28:23 Access to genetic testing in inherited retinal diseases and remaining gaps 32:10 Key scientific, regulatory, and commercial challenges facing gene therapy today 35:39 Closing remarks Find out more: Beacon Therapeutics Please consider rating and reviewing us on your chosen podcast listening platform! 

This week on The Genetics Podcast, Patrick is joined by Zornitza Stark, Professor at the University of Melbourne and Co-Group Leader at the Murdoch Children’s Research Institute. Using early findings from the BabyScreen+ genomic newborn screening study, they examine feasibility, clinical impact, and family-wide implications beyond standard screening, and consider what these insights mean for infrastructure, policy, and equitable implementation at scale. Show Notes:  0:00 Intro to The Genetics Podcast 01:00 Welcome to Zornitza 01:55 Methods and findings of the BabyScreen+ study  04:35 Scaling the BabyScreen+ study from pilot to population screening 07:46 Balancing benefits, risks, and downstream implications in genomic newborn screening 15:55 How the genes tested in BabyScreen+ were selected 19:00 Cascade testing and the family-wide implications of genomic newborn screening 22:05 What large-scale genomic newborn screening could reveal about penetrance  23:57 Expanding genomic newborn screening over time and addressing equity, scale, and long-term value 27:47 Rapid genomic sequencing in critically ill newborns from pilot studies to national implementation 34:32 Building evidence infrastructure to interpret variants and support reimbursement decisions 37:25 Why global data sharing in genomics requires policy alignment and sustained infrastructure investment 39:55 Current priorities and the future direction of genomics in Australia 42:14 Closing remarks Find out more: BabyScreen+ study Please consider rating and reviewing us on your chosen podcast listening platform! 

This week on The Genetics Podcast, Patrick is joined for a special recording at the Flagship Pioneering studio during JPM 2026 by Michelle Werner, CEO of Alltrna, and Mike Severino, CEO of Tessera Therapeutics. They discuss the molecular mechanisms behind Alltrna’s engineered tRNA and Tessera’s gene-writing platforms, why 2026 marks a major inflection point as both programs enter the clinic, and considerations around trial design, patient needs, and delivering therapies at scale. Show Notes:  0:00 Intro to The Genetics Podcast 00:59 Welcome to Michelle and Mike 01:26 Overview of Alltrna’s therapeutic approach to rare genetic diseases using engineered tRNAs 03:19 Overview of Tessera Therapeutics’ gene writing approach 04:51 Preclinical evidence supporting first-in-human testing of Alltrna’s lead candidate 07:50 Why Tessera’s preclinical models are predictive of clinical success 10:40 Key features that differentiate Tessera’s RNA-based gene writing 14:02 Advantages of using basket trials for engineered tRNAs 18:00 Clinical trial design and early efficacy signals for gene writing in alpha-1 antitrypsin deficiency 21:59 Genetic testing, patient identification, and patient advocacy in Alltrna trials 24:18 Differentiating Tessera’s gene writing approach for patients and investigators 26:35 Site readiness and expertise required for genetic medicine trials 28:32 Scaling Alltrna’s platform across mutations, tissues, and diseases 32:34 Expanding Tessera’s gene writing platform beyond alpha-1 antitrypsin deficiency 35:57 Perspectives on biotech funding, pharma partnerships, and rare disease investment 39:08 The data pharma looks for when partnering on novel genetic therapies 42:49 Emerging technologies Michelle and Mike are watching beyond their own platforms  47:19 Closing remarks Find out more: Alltrna (https://www.alltrna.com/) Tessera Therapeutics (https://www.tesseratherapeutics.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 Dr. Travis Hinson, Professor and physician at the University of Connecticut and investigator at the Jackson Laboratory. They discuss how genetics is reshaping the understanding of heart failure, why sarcomere biology has become a central target for new gene-based therapies, and how advances in genome editing and preventive genetics could redefine cardiovascular care. Show Notes:  0:00 Intro to The Genetics Podcast 01:00 Welcome to Travis 01:44 Overview of gene editing for inherited cardiovascular disease 05:01 Delivery methods and viral capsid engineering to target heart tissue 07:29 Role of the titin gene in dilated cardiomyopathy and treatment opportunities 10:32 Genetic variants in titin and differences in phenotype 13:51 Promising therapeutic approaches for targeting titin  16:21 Possibility of using a mini titin gene for replacement 17:31 Sarcomere proteins and their role in cardiomyopathy 20:28 Limits of current understanding in heart failure, including cardiac regeneration and congenital heart disease 24:50 Predicting drug-induced cardiotoxicity using stem cell models, animal studies, and digital twins 30:02 How Travis balances clinical genetics at the University of Connecticut with translational research at the Jackson Laboratory (JAX) 32:03 Where genetic testing is used in cardiology today and what’s limiting broader access 35:19 Understanding polygenic risk and unexplained heritability in cardiovascular disease 37:07 Managing inherited cardiomyopathy risk in families after a pathogenic variant is identified 40:36 Genetic testing as a prevention strategy and the public health case for earlier intervention 43:03 Balancing early genetic screening with penetrance, uncertainty, and patient anxiety 45:51 Closing remarks Find out more: Review on cardiovascular gene editing approaches Please consider rating and reviewing us on your chosen podcast listening platform!