In the latest episode of The Genetics Podcast, Sano CEO Patrick Short had a fascinating conversation with Michelle Werner, CEO of Alltrna and CEO/Partner at Flagship Pioneering. Michelle and her team are pushing the boundaries of tRNA therapies, aiming to provide scalable treatment options for people with rare and ultra-rare diseases.
Understanding stop codon diseases and tRNA therapies
Michelle kicked off by explaining stop codon diseases, which result from nonsense mutations that create shortened or absent proteins. These mutations are surprisingly common, affecting about 30 million people worldwide. Alltrna is addressing this issue by engineering transfer RNAs (tRNAs) to bind to these premature stop codons, effectively allowing cells to produce full-length, functional proteins again.
What makes Alltrna’s approach so unique is its universality. Unlike traditional gene therapy methods that tackle diseases on a gene-by-gene basis, Alltrna's engineered tRNAs can address the root cause across many different genetic conditions. With just 19 engineered tRNAs needed to cover all stop codon mutations, they are pioneering a precise and efficient genetic correction method.
Delivery challenges and driving innovation
The conversation then turned to the practical aspects of delivering these therapies. Michelle discussed the use of lipid nanoparticles to deliver tRNAs to the liver and mentioned their exploration of various other delivery mechanisms. She also introduced the concept of basket trials, which group patients based on genetic mutations rather than specific diseases. This approach could accelerate the development and approval process for multiple genetic conditions at once.
The regulatory landscape was also a topic of discussion, with Michelle emphasising the importance of early and frequent interactions with health authorities.
Looking ahead: Future directions and collaboration
Michelle discussed the future of tRNA therapies, including potential new delivery methods and expanding clinical trials. She highlighted the importance of collaborating with patient advocacy groups, academic experts, and industry partners to advance these therapies and ensure they reach the patients who need them most.
And speaking of patients who need them most: Michelle also touched on her personal motivation for this work, her son's diagnosis with Duchenne muscular dystrophy. This personal connection fuels her dedication to finding effective therapies for rare diseases and drives her to push boundaries.
Summary
Patrick’s chat with Michelle Werner was an inspiring look into the cutting-edge work being done at Alltrna. The potential of tRNA therapies to treat a wide range of genetic diseases is a game-changer in the field of genetic medicine. Michelle’s blend of professional insight and personal passion offers a hopeful outlook for the future of precision medicine.
Listen to the full episode here:
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