Seminar | Restoring Cellular Identity and Reversing Disease through Partial Reprogramming.

2025-12-24

John Rasko AO

On December 22, 2025, Professor John Rasko AO from Altos Labs presented “Gene & Cell Therapies: Translating biological discoveries to cures.” The presentation examined the evolution of genetic medicines and the translational pathways required to move benchside discoveries into clinical applications

Professor Rasko first elucidated the role of “intron retention” as a pivotal mechanism for gene regulation via nonsense-mediated decay (NMD). This foundational work, published in Cell, provides a sophisticated framework for understanding hematopoietic maturation and the molecular drivers of cancer.

The seminar also highlighted the clinical success of the Cymerus™ platform in producing iPSC-derived mesenchymal stem cells (MSCs). Results from the landmark trial for steroid-resistant aGVHD demonstrated the long-term safety and scalability of these "off-the-shelf" cellular products. Addressing the limitations of viral-mediated therapies, Professor Rasko shared long-term data from Hemophilia B trials while cautioning against the risks of high-dose AAV vectors. To mitigate these challenges, he introduced ABR2—a novel AAV co-receptor identified via CRISPR screening. By enhancing transduction efficiency 5- to 10-fold, this discovery offers a strategic path to reducing viral dosages, lowering costs, and improving patient safety.

Professor Rasko concluded by emphasizing that international collaboration and technological optimization remain essential to ensuring these high-cost curative therapies reach global patient populations.

About the speaker

John Rasko AO is a clinical haematologist and Director of the Department of Cell & Molecular Therapies at Royal Prince Alfred Hospital. A preeminent figure in regenerative medicine, he has served as President of the International Society for Cell & Gene Therapy (ISCT) and currently chairs Australia’s Gene Technology Technical Advisory Committee. With over 270 peer-reviewed publications, including landmark trials in hemophilia and thalassemia, Professor Rasko has been instrumental in shaping global regulatory standards. His contributions have been recognized with numerous honors, including the Officer of the Order of Australia.