DNA Today: A Genetics Podcast

CRISPR has carried enormous promise since scientists first realized its potential to edit the human genome, but it has also raised some of the biggest ethical questions in modern genetics. In this episode, Kira Dineen sits down with Dr. Kiran Musunuru to trace the evolution of human gene editing, beginning with the controversial 2018 announcement that scientist He Jiankui had used CRISPR to edit human embryos in China, resulting in the birth of the world’s first gene-edited babies. The experiment, which targeted the CCR5 gene in an attempt to reduce susceptibility to HIV, sparked international condemnation and intensified debate over germline genome editing, where genetic changes could potentially be passed on to future generations. From there, the conversation shifts to a dramatically different application of CRISPR: treating serious genetic disease in an individual patient. Dr. Musunuru shares the remarkable story of Baby KJ, who was born with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency and became the first patient to receive a personalized CRISPR-based therapy designed specifically for his genetic variant. The team developed KJ’s customized base-editing treatment in approximately six months, moving from identification of his variant through preclinical testing, manufacturing, regulatory review, and ultimately treatment. Dr. Musunuru explains how KJ’s therapy works, what researchers have learned from his response so far, and whether his case could establish a new pathway for treating patients with ultra-rare genetic conditions who may never fit into a traditional drug-development model. This interview was recorded in person at AGBT Precision Health in Coronado, California, we caught up with Dr. Musunuru after a presentation. Episode Discussion Topics: The 2018 announcement of the world’s first CRISPR-edited babies in China Why He Jiankui’s experiment targeting the CCR5 gene sparked global scientific and ethical backlash The difference between editing embryos and germline cells versus editing somatic cells in a patient What the CRISPR babies controversy taught the scientific community about oversight, regulation, and responsible use of gene-editing technology How the field of CRISPR medicine has evolved since 2018 How naturally occurring PCSK9 variants helped reveal a powerful target for lowering LDL cholesterol and preventing cardiovascular disease Using CRISPR base editing to permanently turn down PCSK9 activity in the liver as a potential one-time treatment for high cholesterol The development of PCSK9 gene-editing therapies for patients with familial hypercholesterolemia and premature coronary artery disease The possibility of moving cardiovascular care from lifelong medications to durable, one-time genetic treatments How cardiovascular gene editing helped pave the way for applying similar base-editing technology to rare diseases like Baby KJ’s CPS1 deficiency What CPS1 deficiency is and why it can become life-threatening shortly after birth How Baby KJ’s diagnosis created an opportunity to pursue a personalized gene-editing treatment Why KJ’s specific genetic variant was a candidate for base editing How base editing differs from traditional CRISPR approaches that make double-stranded breaks in DNA Developing a gene-editing therapy specifically for a single patient Delivering the gene editor to liver cells using lipid nanoparticles Why the liver is an especially promising target for in vivo gene-editing therapies The collaboration between researchers, clinicians, biotechnology companies, regulators, and KJ’s family that made the treatment possible Navigating FDA review for a therapy that had never previously been given to a human Why KJ received multiple doses of the therapy Early signs that the treatment was having an effect, including increased dietary protein tolerance and reduced dependence on nitrogen-scavenging medication Why researchers are careful not to describe KJ’s treatment as a cur

Please note this episode is only available on our website, DNAToday.com under Episode 415, and access is limited to those in the United States. In just a few years, achondroplasia treatment has expanded from no approved precision medicines to multiple approaches targeting the condition’s underlying biology. In this episode, we continue our conversation with Dr. Ravi Savarirayan, a global leader in skeletal dysplasia care and a lead investigator across multiple achondroplasia clinical development programs. Dr. Savarirayan previously joined us on Episode 401, where we explored the first approved precision treatment for achondroplasia and international guidance for its use. This time, we take a broader look at the rapidly evolving achondroplasia treatment landscape, including how different therapeutic approaches target FGFR3 signaling, how researchers interpret clinical trial outcomes, and what results from the Phase 3 PROPEL 3 study of investigational infigratinib could mean for children and families. We also discuss why treatments cannot be reliably compared using results from separate clinical trials, the importance of studying outcomes beyond growth, and the questions that remain about long-term safety, functional benefits, treatment selection, and switching therapies. Thank you to BridgeBio for sponsoring this episode. Episode Discussion Topics How the achondroplasia treatment landscape has evolved in the last seven years How achondroplasia affects more than height How current and investigational therapies target FGFR3 signaling in different ways What annualized growth velocity, height Z-scores, and body proportionality reveal in clinical trials Key findings from the Phase 3 PROPEL 3 study of investigational infigratinib What researchers can and cannot yet predict about final adult height based on current data Why body proportionality may be an important clinical and functional outcome How researchers are evaluating potential effects on mobility, reach, independence, and daily activities The long-term safety questions that remain when treatment begins in childhood Why results from separate achondroplasia trials should not be compared directly How families and healthcare providers can weigh treatment benefits, risks, administration, and personal goals What is being studied in hypochondroplasia and other conditions involving overactive FGFR3 signaling Our Guest: Dr. Ravi Savarirayan Ravi Savarirayan is consultant clinical geneticist at Victorian Clinical Genetics Services, Professorial fellow at the University of Melbourne, and Group leader (Molecular Therapies at Murdoch Children’s Research Institute, Victoria, Australia. Professor Savarirayan received his MBBS from the University of Adelaide, Australia in 1990 and became a Fellow of the Royal Australasian College of Physicians in 1997. He was certified as a specialist in Clinical Genetics by the Human Genetics Society of Australasia in 1998 and was awarded his Doctor of Medicine from the University of Melbourne in 2004. He was awarded the Fulbright Professional Scholarship for Australia in 1998, and took this up at University of California, Los Angeles (UCLA). Professor Savarirayan’s primary research focus is on inherited disorders of the skeleton causing short stature, arthritis, and osteoporosis. He has published over 230 peer-reviewed articles and received over $35M in research funding, collaborating with researchers from 40 countries. His current clinical trial activities are pioneering disruptive new therapies for the treatment of genetic disorders. He was the global lead investigator of the clinical development program that identified vosoritide as the first precision therapy for children with achondroplasia. He was recently named one of the 30 “Brilliant minds” of the Murdoch Children’s Research Institute over the past 30 years, was awarded the Institute’s research excellence award in 2020, and is an NHMRC Leadership Fellow. Resources BridgeBio Acho

When patients relocate or relatives living abroad need cascade testing, finding a qualified genetics professional in another country can be surprisingly difficult. The new Global Genetics Directory aims to change that through a free, verified, peer-to-peer resource connecting genetics and genomics professionals worldwide. In this episode of DNA Today, recorded in person at our studio, host Kira Dineen is joined by genetic counselor Monisha Sebastin, Founder and Principal Investigator of the Global Genetics Directory. Monisha explains how her international background and leadership within the genetics community revealed the need for a centralized global resource. We explore how the directory was developed with support from the prestigious Audrey Heimler Special Projects Award, how professionals are verified across different credentialing systems, and why the team chose a closed, consent-based model rather than a publicly searchable directory. Monisha also shares how the directory could strengthen cross-border patient care, cascade testing, professional collaboration, and access to genetics services around the world. Episode Discussion Topics Why finding genetics professionals in other countries can be challenging How Monisha’s experiences in India and the United States shaped her perspective on global access When international connections are especially important for patient care and cascade testing What genetics professionals around the world said they needed from a global directory How NSGC’s Audrey Heimler Special Projects Award supported the project How registration, credential verification, and directory searches work Why eligibility is limited to credentialed genetics and genomics professionals How the directory accommodates differences in professional titles, credentials, and scopes of practice Why membership is free The benefits of a closed, peer-to-peer, and consent-based model How patients seeking care abroad can work with their current providers The team’s vision for expanding the directory and strengthening international collaboration About Monisha Sebastin Monisha Sebastin, MS, LCGC, is the Founder and Principal Investigator of the Global Genetics Directory. She is also a senior pediatric genetic counselor in New York City, where she specializes in cardiogenetics and research. Monisha grew up in India and earned her undergraduate degree in genetic engineering before completing her genetic counseling training at Sarah Lawrence College. Her international background, clinical experience, and leadership within the global genetic counseling community helped inspire the development of the Global Genetics Directory. The directory was developed with support from the Audrey Heimler Special Projects Award for Monisha’s project, “Evaluating International Genomics Providers’ Needs and Perspectives on a Global Genomics Services Directory.” Resources & Links Global Genetics Directory To email directly, [email protected] National Society of Genetic Counselors (NSGC) NSGC’s Audrey Heimler Special Projects Award Find A Genetic Counselor Directory Relevant DNA Today Podcast Episodes #109 Shenela Lakhani on Genetic Counseling in Qatar — Hear from Qatar’s first certified genetic counselor about establishing the profession in a new country and adapting counseling across cultures. #110 Gattaca, 22 Years Later with Catherine Mayo and Ale Cantu — Catherine Mayo’s first DNA Today appearance examines the film’s enduring relevance to genetic counseling, reproductive decision-making, and genetic discrimination. #114 Matt Burgess on Australasian Genetic Counseling — Explore genetic counseling education, certification, private practice, and healthcare delivery in Australia and across the Australasian region. #212 NSGC Recap 2022 — Meet Monisha and learn about the clinical care and compassion that earned her the Heart of Genetic Counseling Award, along with her work supporting international genetic coun

For most people, eating is an ordinary part of the day. But when you have phenylketonuria (PKU), every meal can involve calculations, preparation, medical monitoring, and decisions that affect how your brain and body feel. This is DNA Today, a podcast from Gene Pool Media, where we explore the breakthroughs, challenges, and human impact of genetics and genomics. I’m your host Kira Dineen, a genetic counselor and award-winning science podcaster and speaker. This is a continuation of our PKU series, sponsored by PTC Therapeutics. In the first episode (Episode 399), we explored how PKU helped launch newborn screening and why early diagnosis can completely change a child’s future. In this second episode, we’re looking at what comes next: what it actually means to manage PKU through food, and how this affects school, friendships, celebrations, mental health, independence, and a person’s relationship with food. Joining us are a mother and daughter who have experienced that journey together: Dr. Jennifer Brown is a geneticist, science communicator, and author of When the Baby Is Not OK: Hopes & Genes, a wonderful memoir about genetics, motherhood, and raising children with PKU. Lillian Isabella is a playwright, advocate, and graduate student in Columbia University's Narrative Medicine program who served six years on the National PKU Alliance board and lives with PKU. She is Dr. Brown's daughter. Our guests are participating in this podcast to share their experience and opinions only. They are not providing any medical advice. Always check with your healthcare provider for treatment and screening advice. Episode Discussion Topics What a “low-protein diet” actually requires for someone living with PKU How protein and phenylalanine tolerance are determined and monitored over time The work involved in grocery shopping, measuring food, reading labels, preparing specialized meals, and ordering medical foods Dr. Brown’s experience learning to treat feeding her newborn as a form of medical care Raising two daughters with PKU and balancing dietary management with everyday family life Lillian’s relationship with PKU formula and medical shakes throughout different stages of life How elevated phenylalanine levels can affect focus, energy, mood, and daily functioning Navigating school, birthday parties, holidays, camps, travel, dating, and other food-centered social situations When Lillian first became aware that she ate differently from her peers How constant food monitoring can influence a person’s emotional relationship with eating PKU-related frustration, burnout, anxiety, guilt, and resentment How language used by clinicians can shape a child’s identity and relationship with their condition Transitioning from parent-managed PKU care to greater independence in adolescence and adulthood Returning to metabolic care after time away Lillian’s experience turning her lived experience with PKU into advocacy Advice for parents who have just learned their baby has PKU How guidance and support may change through early childhood, adolescence, and adulthood Dr. Brown and Lillian’s hopes for the future of PKU care and what could make everyday management easier Resources & Links When the Baby Is Not OK: Hopes & Genes by Dr. Jennifer Brown PKU / Phenylketonuria Phenylalanine hydroxylase deficiency ACT Sheet The Newborn Screening Information Center (NBSIC) Recommended Uniform Screening Panel, or RUSP RUSP overview for families ACMG Newborn Screening ACT Sheets and Algorithms Baby’s First Test: Newborn Screening Information National PKU Alliance Relevant DNA Today Podcast Episode Episode 399: PKU and the History of Newborn Screening – In the first installment of this series, we explore how PKU helped launch newborn screening and why early diagnosis can dramatically change a child’s future. Connect with DNA Today: You never have to wait long for a new episode of DNA Today, we release episodes every Friday! In the meantime, exp

Prenatal cell-free DNA screening is designed to assess a pregnancy for chromosome conditions; but in rare cases, it can reveal something entirely unexpected about the pregnant patient’s own health. In this episode, Kira Dineen is joined in-person by Dr. Diana Bianchi to explore how unusual or non-reportable cfDNA screening results can sometimes be a signal of an undiagnosed maternal cancer. Dr. Bianchi shares findings from the NIH’s ongoing IDENTIFY study, which is investigating why these unexpected cfDNA patterns occur, how clinicians can distinguish potential malignancy from other explanations, and what should happen next when a prenatal screening result raises concern about maternal cancer. We recorded this episode in person at AGBT Precision Health, one of our favorite conferences of the year. The conference wrapped this past Wednesday and brought together leaders across genomics, precision medicine, research, and clinical care in an intimate setting that makes it easy to connect, learn, and have thoughtful conversations. The conference is also hosted at a beautiful resort in the San Diego area, which makes the experience especially memorable. We highly recommend attending next year’s AGBT Precision Health meeting, taking place September 13–15, 2027, at the same gorgeous location. We already put it on our calendars! In This Episode, We Discuss: What “non-reportable” or “uninterpretable” cfDNA results actually mean How unusual cfDNA results differ from typical test failures Determining whether an unexpected cfDNA signal originates from the fetus, placenta, or pregnant patient Maternal causes of discordant cfDNA results, including fibroids, clonal hematopoiesis, a demised twin, and malignancy Why tumors can release DNA into the bloodstream that is detected during prenatal screening Why Dr. Bianchi and her colleagues launched the prospective IDENTIFY study in 2019 What participants undergo when they travel to the NIH Clinical Center for evaluation Results from the first 107 IDENTIFY participants, including the 52 participants diagnosed with cancer Why lymphoma is frequently identified through these unusual cfDNA patterns Chromosomal patterns that are particularly suspicious for malignancy Why gains and losses involving three or more chromosomes can be an important warning sign Why symptoms, physical examinations, and routine bloodwork may not reliably identify patients with occult cancer The role of rapid whole-body MRI in evaluating patients for malignancy Approaches clinicians can consider when whole-body MRI is not readily available Diagnosing and treating cancer during pregnancy What researchers have learned from participants whose evaluation does not identify cancer How the IDENTIFY study has expanded since its original published cohort How laboratories should report cfDNA patterns that may suggest maternal malignancy The need for professional society guidelines for clinicians receiving these unusual results What genetic counselors, OB/GYNs, and maternal-fetal medicine specialists should do when they receive a concerning non-reportable NIPS result About Dr. Diana Bianchi Diana W. Bianchi, MD, is a physician-scientist and a pioneer in noninvasive prenatal genetic testing and fetal cell microchimerism research. She previously served as Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health and was a senior investigator in the Center for Precision Health Research at the National Human Genome Research Institute. Her research has helped define how prenatal cell-free DNA sequencing can unexpectedly identify genomic patterns associated with maternal malignancy. In 2019, Dr. Bianchi and colleagues launched the IDENTIFY Study — Incidental Detection of Maternal Neoplasia Through Non-Invasive Cell-Free DNA Analysis — to investigate the biological causes of unusual or non-reportable prenatal cfDNA results and develop evidence-based approac