Genetic Therapies Bootcamp: Foundations, Frontiers, and Clinical Engagement OnDemand-03-10 12-55 318-323 Larson Session 1 Overview of Genetic Therapies

Video Transcription

Video Summary

Dr. Yu's comprehensive presentation explores the landscape of gene-targeted therapies, focusing on antisense oligonucleotides (ASOs) and related modalities. ASOs, like nusinersen for spinal muscular atrophy, modulate RNA splicing without altering DNA and offer advantages such as simpler manufacturing and re-dosability but require repeated dosing and face tissue delivery challenges. Other oligonucleotides include phosphomorpholinos (PMOs) and siRNAs, exemplified by therapies for Duchenne muscular dystrophy and TTR amyloidosis, respectively. Delivery methods vary between in vivo and ex vivo approaches, each with respective pros and cons in control and safety. AAV vectors are widely used but face immunogenicity, limited packaging capacity, and dosing constraints. The promise of genetic programmability — modular, adaptable drug development — remains partly unrealized across modalities. Clinical trials confront challenges including small patient populations, lack of placebo use, and prolonged outcome latency. Recent regulatory advances like the FDA’s plausible mechanisms pathway may accelerate approval and access. Multidisciplinary collaboration and ethical vigilance remain crucial as gene therapies evolve.

Keywords

antisense oligonucleotides

gene-targeted therapies

nusinersen

AAV vectors

clinical trials challenges

FDA regulatory advances