The Genetics Podcast

Summary: This week on The Genetics Podcast, Patrick is joined by Lisa Gurry, Chief Business Officer of GeneDx. They discuss her path from two decades at Microsoft to leading one of the most influential genomics companies, GeneDx’s mission to deliver the fastest rare disease diagnoses, and how large-scale data, newborn screening, and AI are shaping the future of precision medicine.Show Notes: 0:00 Intro to The Genetics Podcast01:00 Welcome to Lisa and her career path leading to joining GeneDx  03:27 The core components of GeneDx and how they drive early rare disease diagnosis06:18 Insights from early genomic newborn screening pilots11:37 The clinical impact and economic benefits of newborn genomic screening14:27 How GeneDx combines data, AI, and clinical expertise to improve genomic interpretation17:44 A vision for a lifelong genomic passport and how it could guide care across every stage of life20:42 How GeneDx Infinity is unlocking new therapeutic possibilities in genetically linked autism22:48 How advocacy communities guide patient identification and connect families to opportunities26:00 Lessons from 23 years at Microsoft that Lisa now applies to leading GeneDx30:39 How Truveta emerged from the COVID crisis to build a shared-data platform for population-scale health insights32:13 What excites Lisa most about leading GeneDx and where she sees the biggest opportunities ahead34:59 Closing remarksPlease 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. Jeffrey Chamberlain, Professor at the University of Washington School of Medicine, co-founder of Kinea Bio, and Director of the Muscular Dystrophy Cooperative Research Center of Seattle. They discuss the early breakthroughs that revealed the structure and function of the dystrophin gene, how those insights led to the creation of micro-dystrophin and systemic AAV delivery in Duchenne, and the major scientific and clinical challenges the field must now solve.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Jeffrey01:33 Early discovery of the dystrophin gene and how it shaped Duchenne muscular dystrophy (DMD) research09:07 Efforts to map dystrophin and develop practical diagnostic techniques12:04 How research in Jeffrey’s lab gradually led to the creation of micro-dystrophin 20:15 How micro-dystrophin and AAV delivery converged into a viable systemic gene therapy strategy27:23 Current successes and safety challenges in systemic AAV gene therapy for neuromuscular disease34:44 Prospects and limitations of gene editing for Duchenne and emerging alternatives to AAV micro-dystrophin44:57 Closing remarksPlease 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 Dr. Rachel Salzman, CEO of Armatus Bio. They discuss the promise of vectorized RNAi for autosomal dominant diseases, the key scientific and clinical hurdles in gene therapy, and Rachel’s lessons from two decades in the field.Show Notes: 0:00 Intro to The Genetics Podcast01:00 Welcome to Rachel01:35 Background of Armatus Bio and the mechanism behind its vectorized RNAi platform05:31 Advantages of vectorized RNAi over conventional RNAi approaches08:07 How microRNAs work and how engineered versions enable highly specific gene silencing10:28 Current preclinical progress at Armatus and next steps toward first-in-human trials14:06 Lessons on making smart risk decisions in rare disease drug development17:26 Reflections on two decades of progress, setbacks, and realities in gene therapy22:07 Hemophilia as a case study in gene therapy missteps and overlooked patient and market realities25:21 Challenges around product purity and the need for financial innovation29:23 Why AAV purity is so difficult to achieve and where pre-competitive collaboration could drive improvement33:32 Rachel’s path from veterinary medicine to gene therapy through a family genetic diagnosis35:58 Founding the Stop ALD Foundation and advancing lentiviral gene therapy into first-in-human use39:58 The future potential of vectorized RNAi 42:00 Closing remarksPlease 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 Slavé Petrovski, Vice President of the Center for Genomics Research at AstraZeneca. They discuss how AstraZeneca is scaling population genomics through massive biobank collaborations, developing AI models for early disease prediction, and pioneering sustainable “green” algorithms to reduce the environmental footprint of large-scale genomic research.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Slavé02:09 Slavé’s career path from business information systems to genomics04:33 How Slavé decided to move from academia to industry07:52 Scaling and diversifying biobank partnerships to unlock new genetic insights12:29 Translating biobank data into predictive and preventive medicine15:14 Discovering protective genetic variants through global biobank studies19:13 Leveraging population genetics to identify and validate protective drug targets23:52 Developing an AI tool (MILTON) for integrating multi-omic and clinical data for early disease prediction28:12 Redefining clinical trials in a presymptomatic and predictive medicine era30:49 AstraZeneca’s efforts to make large-scale genomics computing sustainable through green algorithm innovation39:05 AstraZeneca’s open science strategy and global impact of its shared genomics tools42:10 Fostering critical thinking and avoiding groupthink in large-scale genomics research45:30 Looking ahead to the next decade of genomics and precision healthcare50:01 Closing remarksFind out moreMILTON (https://www.astrazeneca.com/r-d/our-technologies/machine-learning-drug-discovery.html)PheWAS Portal (https://azphewas.com/)Upcoming webcast with deep dive into MILTON & PheWAS (https://www.nature.com/articles/d44224-025-00033-7)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. Ellen Reisinger, Professor and group leader at the University of Tübingen. They discuss her journey into hearing loss research, why otoferlin has become a leading target for gene therapy, and the emerging science shaping the next generation of treatments.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Ellen01:52 Ellen’s career path that coincidentally led to her work on otoferlin-related hearing loss03:22 Mechanism and advantages of the dual adenoassociated virus (AAV) system 05:35 The genetic landscape of early-onset hearing loss and why otoferlin stands out07:42 Why otoferlin-related deafness is an ideal target for postnatal gene therapy development09:53 Potential next gene therapy targets beyond otoferlin and associated challenges13:13 Carrier and newborn screening as approaches to preventing hereditary hearing loss14:37 How far the field is from prenatal gene therapy and why it remains unlikely in the near term16:07 Exploring gene-agnostic and protective approaches to prevent or slow hearing loss18:22 How genetics and environment interact in age-related hearing loss20:00 Current research focus of Ellen’s group on degenerative hearing loss genes and uncovering cell death mechanisms22:05 Using mouse models and human organoids to study hearing loss mechanisms23:42 Emerging gene editing approaches 25:20 Ellen’s research journey from biochemistry to leading gene therapy research in hearing loss 27:54 Unanswered questions about how inner hair cells release neurotransmitters29:21 Comparing outcomes of gene therapy and cochlear implants for hearing restoration and differences across languages34:20 Closing remarksPlease 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 BridgeBio’s Ananth Sridhar, Chief Operating Officer of Cardiorenal Programs, and Sun-Gou Ji, Vice President of Computational Genomics. They discuss the hub-and-spoke model for de-risking and accelerating rare disease drug development, the role of human genetics in target discovery, lessons from their autosomal dominant hypocalcemia type 1 (ADH1) program, and how portfolio design and predictive genomics are shaping the future of precision medicine.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Ananth & Sun-Gou01:57 How BridgeBio’s hub-and-spoke model de-risks and accelerates rare disease drug development06:45 How programs move from the hub to the spokes in target discovery and development09:10 Translating a target into a therapy for autosomal dominant hypocalcemia type 1 (ADH1)12:28 Challenges in ADH1 drug development and using population genetics to identify patients with gain-of-function variants18:08 Under-diagnosis and incomplete penetrance in rare disease and quantifying genetic versus phenotypic prevalence20:52 Balancing first-in-class innovation with risk management in rare disease drug development24:24 Evaluating rare disease programs using risk-adjusted net present value (NPV) instead of peak sales27:20 Key factors that can make rare disease programs faster and cheaper to develop, and why modality agnosticism is important32:00 Sun-Gou’s experience in computational genetics and building data-driven infrastructure for discovery36:44 Ananth’s lessons from Regeneron and applying patient-centered principles to rare disease drug development39:00 Sun-Gou on the power of newborn sequencing and personal lessons from early diagnosis43:36 Ananth’s views on making predictive medicine more personal and human-centered44:51 Closing remarksFind out moreBridgeBio (https://bridgebio.com/unlocking-rare-diseases-medicine)Hub-and-spoke model (https://www.youtube.com/watch?v=gRURL49QsX4)ADH1 publication (https://www.cell.com/ajhg/fulltext/S0002-9297(25)00244-7)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 Justin Porcano, co-founder and Executive Director of Save Sight Now. They discuss how his daughter’s diagnosis with Usher syndrome type 1B (USH1B) inspired the founding of Save Sight Now, the organization’s efforts to accelerate research and overcome barriers in gene therapy, and the innovative gene delivery methods and therapeutic approaches currently in development.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Justin01:39 How Justin’s daughter’s Usher syndrome diagnosis (USH1B) led to the founding of Safe Sight Now and a mission to accelerate research05:23 Biggest hurdles to therapeutic development for USH1B08:36 Progress in the research with new animal models and advances in clinical endpoint development10:25 How Justin applied design thinking and AI to rapidly learn rare disease science12:38 Advances in gene delivery approaches for USH1B15:45 Therapeutic intervention windows in USH1B with early treatment for hearing loss and later options for addressing vestibular and visual impairments18:32 Save Sight Now’s plans for the next phase of clinical translation and sustainable growth20:50 Why Justin decided to establish Save Sight Now as an independent nonprofit22:27 The need for stronger collaboration between patient organizations and biotech companies25:50 Building global collaborations to expand Save Sight Now’s reach28:00 How the community can support Save Sight Now’s mission and upcoming fundraising gala28:59 Closing remarksFind out moreSave Sight Now (https://www.savesightnow.org/)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, recorded live at ASHG 2025, Patrick is joined by Heidi Rehm, Chief Genomics Officer at MGH’s Center for Genomic Medicine and Co-director at the Broad Institute, and Slavé Petrovski, Vice President of AstraZeneca's Centre for Genomics Research. They discuss the rapid progress of large-scale genomics, the barriers to integrating genetic data into healthcare and drug development, and how open collaboration, global data sharing, and a focus on equity are driving more inclusive and impactful genomic discovery.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Heidi and Slavé02:01 Slavé’s role at AstraZeneca and work in genomics-driven R&D 03:24 Heidi’s work at the Broad Institute bridging clinical genomics, rare disease research, and global data-sharing initiatives04:12 Heidi on breaking a Guinness world record for rapid neonatal ICU (NICU) genomics and the shift to open data sharing06:32 Slavé on how large-scale, multimodal human data is transforming genomics research08:10 Heidi’s initiatives to integrate genomics into routine care at hospitals and with primary care physicians11:47 Integrating genomics into clinical trials and healthcare, and enabling global discovery through AstraZeneca’s open data portal15:34 Breaking down legal and logistical barriers to genomic data sharing and centering the patient voice18:40 AstraZeneca’s large-scale plasma proteome study and machine learning models predicting disease onset years before diagnosis21:44 Emerging omics tools advancing rare disease diagnosis24:19 The value and pitfalls of AI in genomics today28:54 Advancing health equity in genomics through data sharing, diverse recruitment, and global collaboration33:40 Progress and challenges in next-generation genetic therapies37:15 Reflections and advice for the next generation entering genomics and data-driven medicine40:44 Audience Q&A51:44 Closing remarksPlease 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 Chris Hopkins, CEO of Glafabra Therapeutics. They discuss how Glafabra is advancing a next-generation cell therapy for Fabry disease, the differences between gene therapy modalities, and the future of cell and gene therapy innovation.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Chris01:28 Overview of Fabry disease and reviving a promising shelved gene therapy03:12 Limitations of current Fabry disease treatments versus Glafabra Therapeutics’ approach05:19 How autologous cell therapy avoids an immune response06:43 Comparing this cell therapy approach to that of Casgevy for sickle cell disease11:28 Expanding Glafabra’s platform to other lysosomal storage disorders through enzyme cross-correction13:47 Comparing autologous cell therapy and AAV in Fabry17:02 Path to clinical development and funding strategy for Glafabra’s lead program19:33 Cost efficiency and trial design advantages of an orphan drug approach21:19 Considerations around comparator groups for Glafabra’s therapy24:11 Underdiagnosis and hidden prevalence of rare diseases 25:53 Other innovations Chris is excited about and expectations for the future of cell and gene therapy31:56 How Chris invented a technique to safely “milk” venomous cone snails37:00 Closing remarks and advice for scientists taking the leap from academia to entrepreneurshipFind out moreGlafabra Therapeutics (https://www.glafabra.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 Short takes a solo deep dive into the current state of gene therapy ahead of next week’s live recording at ASHG. He explores the promise and limitations of adeno-associated virus (AAV) delivery, examples of gene therapies for neuromuscular diseases, and the challenges of balancing safety, cost, and commercial viability in rare diseases. Show Notes: 0:00 Intro to The Genetics Podcast00:59 Episode overview02:50 Definition and scope of gene therapy 04:50 Gene therapy delivery via adeno-associated virus (AAV) and associated challenges and advantages06:40 AAV-based gene therapy and other advanced therapies in spinal muscular atrophy (SMA)10:29 Recent safety concerns around Sarepta Therapeutics’ AAV-based gene therapy for Duchenne muscular dystrophy (DMD)19:30 Commercial viability challenges for rare disease gene therapy24:26 Risk-benefit analysis of gene therapy for rare diseases 28:33 Considerations for optimizing AAV design and delivery routes31:26 Alternative approaches for delivery using viral and non-viral methods36:09 The future of AAV gene therapy41:42 Closing remarksFind out moreUpdate on Sarepta Therapeutics’ gene therapy for DMD (https://www.fiercepharma.com/pharma/sarepta-shares-more-elevidys-safety-data-response-patient-group-fda-petition)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 Andy Singleton, Program Lead of the Global Parkinson’s Genetics Program (GP2), and Sonya Dumanis, COO of the Coalition for Aligning Science. They discuss the creation of GP2, how the initiative is closing representation gaps in genetics, and building global infrastructure and capacity for research.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Sonya and Andy01:50 Aims and overview of the Global Parkinson’s Genetics Program (GP2)03:15 The Aligning Science Across Parkinson’s (ASAP) initiative and how it led to the creation of GP204:37 Gaps in Parkinson’s genetics that inspired the creation of GP207:21 Closing the global representation gap in Parkinson’s genetics08:37 ASAP’s model for long-term resources and adaptive funding11:18 How GP2 overcame pandemic disruptions and data-sharing challenges to grow global capacity15:01 Using harmonized data to compare Parkinson’s with other neurological diseases17:02 Expanding GP2’s scope while keeping Parkinson’s at the core18:42 Using genetics to guide targeted Parkinson’s therapeutics 21:37 Early biomarkers beyond genetics including proteomics and alpha-synuclein seed amplification assay (SAA) to guide therapy timing23:01 Adapting GP2 to incorporate new discoveries and build capacity for functional and longitudinal studies26:54 Insights from GBA variants into gene expression and Parkinson’s risk biology28:24 How GP2’s open access data can be used to power clinical trials and advance drug development31:37 Lessons from GP2 on building sustainable global collaboration and capacity that can be applied across disease areas36:10 Navigating global differences in genetic testing access, regulation, and return of results across the GP2 network38:29 Building coalitions between philanthropy, nonprofits, and industry to sustain large-scale initiatives41:09 The story behind the GP2 tattoos and the team spirit that fuels the program42:23 Closing remarksFind out moreASAP (https://parkinsonsroadmap.org/#)GP2 (https://gp2.org/)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 Wanda Smith, founder of CureGRN. They discuss Wanda’s journey from caring for her mother to driving FTD research, the discovery of progranulin and development of new therapies, the diagnostic odyssey and need for earlier genetic testing, and how the CureGRN community is expanding support and awareness worldwide.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Wanda02:18 Wanda’s journey into frontotemporal dementia (FTD) research from being a caregiver to establishing a brain bank06:31 Shifting focus after the discovery of progranulin (GRN) and accelerating FTD research through collaboration08:23 How GRN haploinsufficiency drives FTD and what it means for therapy11:57 Implication of progranulin in neurodegenerative diseases and therapies now in clinical trials13:33 Why earlier genetic testing and diagnosis are critical for families with GRN mutations15:31 Barriers behind the diagnostic odyssey and limited access to genetic testing17:03 Moving from symptom-based diagnosis to early diagnosis with biomarkers19:50 Expanding CureGRN’s reach through global collaboration21:14 Raising awareness to drive FTD research 22:44 Overcoming stigma and shame to encourage trial participation in FTD24:41 Navigating family conversations about FTD with compassion and meeting people where they are26:39 Providing multiple pathways for families to access support, education, and community28:35 Insights into the future of FTD and addressing the gaps preventing progress in care and diagnosis30:58 The importance of genetic testing and community resources in FTD33:23 The role of younger gene carriers in shaping early detection, prevention, and long-term care in FTD37:00 Closing remarksFind out moreCureGRN (https://www.curegrn.org/)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 Terry Pirovolakis, CEO and Founder of Elpida Therapeutics. They discuss Terry’s journey to create a life-saving gene therapy for his son, the founding of Elpida Therapeutics to bring hope to families with ultra-rare diseases, and the challenges of scaling therapies that aren’t commercially viable.Show Notes: 0:00 Intro to The Genetics Podcast00:58 Welcome to Terry01:24 The beginning of Terry’s gene therapy journey after his son Michael was diagnosed with SPG5003:24 Learning the biotech industry and building a gene therapy team05:17 Terry’s experience with learning about gene therapy without a scientific background06:42 The process of building a gene therapy in under three years during the COVID-19 pandemic09:30 Fundraising through community support and major donors11:06 Expanding access of Michael’s gene therapy to children all over the world12:32 The creation of Elpida Therapeutics to develop non-commercially viable therapies and adapting to a challenging funding landscape15:24 Insight into cost, accessibility, and the role of endpoints and manufacturing20:06 Learning from safety events as gene therapy scales and the importance of considering the risk/reward ratio in rare disease23:24 Landscape of precision therapeutics available today beyond AAV vectors27:09 Designing trials at Elpida to demonstrate efficacy in ultra-rare disease29:24 Adapting meaningful endpoints to disease progression and FDA flexibility 34:02 Background of Priority Review Vouchers and the negative impact of its non-renewal on rare disease funding37:48 Finding optimism in rare disease family initiatives and gene therapy successes, and the future of advanced therapeutics 41:07 How to support the rare disease community and families 44:16 Closing remarksFind out moreElpida Therapeutics (https://www.elpidatx.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 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

This week on The Genetics Podcast, Patrick is joined by Benny Sorensen, CEO of Hemab Therapeutics. They discuss how Hemab is reimagining clotting therapies by centering patient voices, how persistence and being “unreasonable” led to their first program, and the value of their multi-modality and collaborative approach.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Benny01:49 Reimagining blood clotting therapies by listening to lived experience and embracing the biotech revolution04:27 How persistence and patient voices sparked Hemab’s first drug development program07:13 Overview of Glanzmann Thrombasthenia (GT) and Hemab’s antibody-based approach10:09 Evolution of hemophilia treatment and neglected blood clotting disorders14:18 Genetic and gender considerations around bleeding disorders17:41 Hemab’s range of therapeutic modalities and the value of collaboration 21:00 Why deep domain expertise drives Hemab’s strategy and success22:55 Lessons from the drug development process24:16 Global insights into gender bias, health inequality, and bleeding disorder care26:46 Upcoming milestones at Hemab 29:52 Lessons from running natural history studies to capture the patient experience33:25 Redefining the patient journey through data34:40 How Benny’s experience at Alnylam Therapeutics shaped his “unreasonable” leadership38:16 Reflections on being a father and a CEO 40:38 Closing remarks and Benny’s commitment to thoughtful drug developmentFind out moreHemab Therapeutics (https://www.hemab.com/)Hemab trial register (https://shorturl.at/8AAQN) 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