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 Podcast

00:59 Welcome to Richard

01:33 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 incentivization

11:15 Building post-approval systems into the genomic medicine lifecycle

14:47 Rethinking evidence standards in rare disease trials, and the global push for regulatory and reimbursement alignment

20:28 Genetic medicine breakthroughs in central nervous system diseases

22:25 The challenges of starting clinical development with an end in mind

24:34 The need for careful analysis around endpoints, vector design, and delivery approaches

29:33 Navigating regulatory hurdles when making mid-program changes to vectors or payloads

31:16 Strategies for enhancing scalability and quality of gene therapy manufacturing 

36:05 Exploring other delivery methods beyond AAV

39:32 Getting ready for the Timmerman Traverse and raising nearly $1M for Life Science Cares

43:48 A call to refocus on patients, partnership, and purpose in uncertain times

45:55 Closing remarks 

Find out more

• Astellas (https://www.astellas.com/)

• Timmerman Traverse fundraising for Life Science Cares (https://timmermantraverse.blackbaud-sites.com/)

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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 Podcast

00:59 Overview of episode content and guests featured

01:47 Eric Topol predicts the role of AI in healthcare in 2019

05:58 Patrick’s reflections on AI’s progress today and future potential

06:57 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 Biobank

18:20 Patrick on the lasting impact of open science and the UK Biobank

19:10 Daphne Koller on building insitro to fuse biology and machine learning

24:30 Patrick on the future of large-language models in biology

25:55 Vineeta Agarwala on investing in large datasets for drug discovery

32:24 Patrick on applying multi-omic data to rare disease research

32:52 Closing remarks

Find out more

The Genetics Podcast is now on Instagram! Follow us for clips from recent episodes and release announcements (https://www.instagram.com/thegeneticspodcast/).

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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 Podcast

00:58 Welcome to Xin 

01:52 Overview of in vivo Perturb-seq

05:10 Identifying de novo variants in autism spectrum disorder

09:00 Using perturbations to map how autism-linked mutations affect specific brain cell types

13:04 Applying Perturb-seq to other brain diseases

14:30 In vivo versus in vitro models and extending genetic screening approaches beyond the brain

18:44 Using in vivo models to trace variant effects, rank gene drivers, and uncover therapeutic pathways

22:35 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 botany

29:48 Xin’s path from China to MIT and how early research shaped her scientific mindset

31:58 Reflections on AI’s rapid progress and limits in biology, and the need for new models 

37:21 Closing remarks

Find out more

• Jin lab (https://www.jin.scripps.edu/)

• In vivo Perturb-seq explainer video (https://vimeo.com/549737357)

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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 Podcast

00:59 Welcome to Benny

01:49 Reimagining blood clotting therapies by listening to lived experience and embracing the biotech revolution

04:27 How persistence and patient voices sparked Hemab’s first drug development program

07:13 Overview of Glanzmann Thrombasthenia (GT) and Hemab’s antibody-based approach

10:09 Evolution of hemophilia treatment and neglected blood clotting disorders

14:18 Genetic and gender considerations around bleeding disorders

17:41 Hemab’s range of therapeutic modalities and the value of collaboration 

21:00 Why deep domain expertise drives Hemab’s strategy and success

22:55 Lessons from the drug development process

24:16 Global insights into gender bias, health inequality, and bleeding disorder care

26:46 Upcoming milestones at Hemab 

29:52 Lessons from running natural history studies to capture the patient experience

33:25 Redefining the patient journey through data

34:40 How Benny’s experience at Alnylam Therapeutics shaped his “unreasonable” leadership

38:16 Reflections on being a father and a CEO 

40:38 Closing remarks and Benny’s commitment to thoughtful drug development

Find out more

• Hemab Therapeutics (https://www.hemab.com/)

• Hemab trial register (https://shorturl.at/8AAQN) 

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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

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 Podcast

00:58 Welcome to Heiko

01:41 Heiko’s career path and how he became interested in medical genetics and therapeutic development

05:49 Connecting the dots across biobanks for genetic discovery

08:23 Heiko’s discovery of a potential gene target for age-related macular degeneration

15:29 The challenge of biobank recontact and why it’s essential for follow-up studies

18:57 The opportunity for smaller companies to follow up on large-scale genomic discoveries

23:00 Advances in cell-based models for neuroscience drug discovery

24:40 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 discovery

30:36 Using cell-based phenotypes to functionally test disease mechanisms and validate variants

33:58 The potential of AI for refining phenotypes and generating drug hypotheses

36:47 Heiko’s advice to early career professionals interested in the field of genetics and drug discovery

38:26 Closing remarks 

Find out more

• insitro (https://www.insitro.com), study on CFHR5 (https://www.nature.com/articles/s41467-025-61193-3)

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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 Podcast

00:59 Welcome to Molly

01:42 Persistent barriers in precision medicine

04:54 Limitations of multiomics technologies and the unique advantage of Element’s approach

07:33 How Element started by inventing an ambitious sequencing instrument

11:33 Overview of the chemistry behind Element’s sequencing technology

14:41 Sequencing workflow of Element’s technology and technical advantages

18:24 Sequencing inside cells and drug discovery insights from a study on tyrosine kinase inhibitor (TKI) resistance pathways

25:57 Sequencing for CRISPR perturbation and direct genotype–phenotype linkage in the same cell

27:33 Whole-transcriptome in situ sequencing and applications in patient samples

29:19 Simplifying single-cell transcriptomics with direct in-sample sequencing

30:31 Applying the single-cell spatial technology to different steps of the drug discovery process

36:43 Competition in the sequencing industry and recent news about Illumina filing a patent infringement case against Element

38:43 Lessons from building Element over eight years

40:32 Insight into maintaining a cohesive culture as Element has multiplied in size and across countries

42:06 The importance of input data quality for AI applications and excitement about the possibility of predicting biology

45:40 Closing remarks

Find out more

• Element Biosciences (https://www.elementbiosciences.com/)

• Pre-print (https://www.biorxiv.org/content/10.1101/2025.05.06.652479v1)

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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 Podcast

00:59 Welcome to David 

01:57 David’s experiences at companies that developed RNA interference (RNAi) and CRISPR technologies

04:05 Lessons from translating RNAi to the bedside 

05:58 The scalable chemistry of RNA versus the complexity of gene editing

07:48 Insight into the lack of rapid scalability and growth in gene therapy companies

09:19 How CAMP4 is using regulatory RNAs to boost gene expression in haploinsufficient diseases

13:01 Mapping and predicting the impact of specific regulatory RNAs on the expression of target genes

15:05 Why regulatory RNAs open up new target space without needing new drug modalities

16:27 How CAMP4 prioritizes certain diseases based on delivery feasibility and genetic evidence

18:31 Understanding expression thresholds in haploinsufficiency and building confidence in therapeutic targets

20:29 Comparing different approaches for increasing gene expression

22:39 Other therapeutic areas of focus for CAMP4, including urea cycle disorders and central nervous system (CNS) disorders

25:47 Lessons from early clinical development and engaging regulators on novel targets

27:47 Building high-resolution regulatory RNA maps beyond what public datasets can provide

31:04 Considerations around the treatment window for SYNGAP1

32:40 The value of collaborative frameworks for rapid therapy development 

35:20 Rethinking early safety assessment and global regulatory strategies for RNA therapies

38:37 The importance of basic science, staying optimistic, and continuing to invest in biotech innovation

40:18 Closing remarks

Find out more

• CAMP4 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 Podcast

00:59 Welcome to Melissa

02:05 Melissa’s career path, beginning with finding her first professorship on Craigslist

04:24 The fundamentals of ontology and how it can help identify common molecular mechanisms across different rare diseases

06:29 Why key rare disease details are missing from electronic health records (EHRs) and how ontologies and AI can help

11:33 How patient self-reporting using layperson phenotypic terms was associated with strong diagnostic performance

15:27 Why recognizing multi-system patterns is key for diagnosing rare conditions and how tools like pattern-based screening are improving outcomes

17:41 How Alamya Health is expanding access to genomic diagnostics by building local lab infrastructure in underserved communities

22:03 How Alamya’s single-test, AI-powered approach helps solve complex cases in underserved settings

24:18 Rethinking the true cost of delayed diagnosis, from wasted testing to the societal and family burden

26:10 What it takes to do national-scale health data research in the U.S. and a vision of real-world data as a public utility

33:37 Opening up access to national EHR data for research through health data networks

36:15 The gap between real-world data and clinical research and why improving data quality benefits both care and science

38:34 A major upcoming milestone in bringing unified rare disease codes into US healthcare with the Mondo ontology

41:22 Closing remarks 

Find out more

• TIS Lab (https://tislab.org/), Alamya Health (https://www.alamyahealth.com/)

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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 Podcast

00:58 Welcome to Frank 

02:00 Origin story for Casma Therapeutics and its therapeutic focus on autophagy

04:51 Diseases in which autophagy is dysregulated

07:46 The link between GBA1 and Parkinson’s, and why so many neurodegenerative diseases exhibit autophagy defects

12:28 Findings from Casma Therapeutics’ preclinical studies and associated mechanisms

16:46 Milestones and design of Casma Therapeutics’ upcoming clinical studies

20:24 Well-characterized cohorts of GDPD patients from natural history studies

21:55 Identifying alternative therapeutic targets involved in autophagy initiation that are mTOR independent

24:46 The negative effects of broad inhibition of mTOR

25:57 Advantages and disadvantages of using small molecule therapy versus broader gene therapy

26:59 Frank’s experience in investment and his approach to risk

29:15 Frank’s perspective on the current biotech climate and how investors view rare disease

32:16 Extending lead candidate and portfolio strategy to other therapeutic applications 

34:15 Partnering opportunities and future potential of the TRPML1 program across neurodegenerative diseases

35:50 A potential link between autophagy pathways and longevity

37:20 Closing remarks

Find out more

• Casma 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 Podcast

00:59 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 Harvard

06:47 Huma’s approach to challenges throughout her journey and how networking helped boost her career

09:30 Ocugen’s mission to develop therapies for retinal disease and recent successes, including obtaining pediatric breakthrough designation

12:10 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 platform

23:17 Therapy mechanism of reactivating degenerating photoreceptors via master regulators 

26:32 Clinical trial design and regulatory considerations

29:15 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 refugees

32:12 Closing remarks and Huma’s message to women and patients

Find out more

• Ocugen (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