Recently on The Genetics Podcast, Patrick sat down with Dr. Erik Ingelsson, Chief Scientific Officer at Wave Life Sciences, to explore some of the most exciting developments in RNA medicine, target discovery, and biotech. With a career spanning academic research, big pharma, and now biotech, Erik shared his unique perspective on advancing genetic discoveries into real treatments for patients.
Wave Life Sciences' work with RNA
Erik begins by introducing Wave's innovative multimodal platform, which spans RNA silencing, splicing, and editing. Unlike DNA editing, which is permanent, RNA editing uses a natural enzyme called ADAR to make precise but reversible changes. This offers a safer and more flexible way to treat genetic diseases.
One of the company’s standout achievements is its RNA editing program for alpha-1 antitrypsin deficiency (AATD). In a world-first, Wave demonstrated successful RNA editing in humans, restoring therapeutic levels of the M-protein in patients after just one dose.
Expanding the reach of RNA therapies
While much of Wave’s work is focused on liver-related diseases like AATD and NASH, they are also expanding into other tissues, including muscle, brain, fat, and lung.
One particularly exciting project is their program targeting obesity by blocking INHBE, a liver-derived hormone that regulates fat storage. The program builds on the discovery that people with natural loss-of-function mutations in the INHBE gene tend to have healthier metabolisms and lower levels of visceral fat. By inhibiting this hepatokine, the treatment aims to regulate fat metabolism more effectively. Preclinical data from Wave indicates that the therapy not only works as a standalone treatment but also enhances the effects of GLP-1 drugs like semaglutide.
From academia to biotech
Patrick and Erik also dive into Erik's career journey—from being a professor at Stanford and Uppsala University to leading genetic research at GSK and now steering innovation at Wave Life Sciences. Erik notes that the biggest difference between big pharma and biotech is focus. At Wave, he and his team work with smaller budgets and tighter timelines, which means prioritizing programs where they have a clear edge.
That focus is paying off. Wave is tackling both novel and well-known genetic targets with fresh approaches. For example, while other companies have struggled to upregulate LDLR or fix PNPLA3 mutations, Wave's RNA editing platform is showing promise in these challenging areas.
Balancing career, curiosity, and family
During the conversation, Erik offered a personal perspective on balancing a high-impact career with family life. He recounted his decision to take two years as a full-time dad while his children were toddlers, emphasizing the importance of being present during their early years. His advice to young professionals? Avoid overworking on weekends, be fully present when spending time with your kids, and remember that the opportunity to spend time with them during their early years is finite. As Erik noted, “At some point, sooner than you think, they’re not that interested in you anymore.”
Looking ahead: the future of RNA editing
As Wave Life Sciences heads into 2025, Erik is optimistic about the expanding potential of RNA medicines. Among the most anticipated developments are the ongoing advancements in their RNA editing programs, including additional clinical readouts for their AATD program.
In addition, Wave is preparing to enter first-in-human trials for new indications, such as their obesity program targeting the INHBE gene. The company is also expanding its pipeline into other challenging areas, including Rett syndrome, cystic fibrosis, and PNPLA3-associated liver diseases, using its RNA editing and silencing platforms to address previously intractable genetic targets.
Listen here:
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