Abstract:
The growth of mRNA as a general platform for biologics is limited by bespoke manufacturing processes that require adaptation across products and scales.
To overcome this barrier to access and innovation, we developed an AI-driven framework that decouples sequence design from manufacturing, analogous to the universal design principles that revolutionized the semiconductor industry, and a brokerage service giving access to highquality, multi-product, multi-scale mRNA manufacturing.
We performed large-scale screens with multiple technologies, from batch to continuous flow developed during the R3 program, quantifying the in vitro transcription (IVT) efficiency of one million diverse sequences. We then trained an interpretable deep learning model that accurately predicts manufacturability from sequences alone and learned underlying molecular mechanisms.
This model, deployed on the brokerage service, prospectively improved the IVT yield of a vaccine and a gene-editing therapeutic by over 7.5-fold. Co-optimization for manufacturability and translation efficiency provided improvements over state-of-the-art commercial mRNA products.
Our AI-driven framework and brokerage services establish a universal design paradigm with the promise to democratize and accelerate the development of mRNA medicines, potentially unlocking a new era in biotechnology.
Biography:
Duccio Medini is a scientist and pharmaceutical executive, currently serving as Chief Science and Technology Officer at Pitt BioForge (Pittsburgh, PA) and as Strategic Data Science Director at Toscana Life Sciences Foundation (Siena, Italy).
He designed and led the Wellcome Leap $60M "R3: RNA Readiness and Response" program, cofunded by CEPI, developing standardized, multi-product, cell-free continuous RNA manufacturing technologies that provide democratized access to diverse biologics and sustainable pandemic response, demonstrated by multiple INDs, and successfully transitioned the program to its second funding cycle, R3 Global.
In executive roles of growing responsibility at Chiron, Novartis and GSK corporations, he led hundreds of data scientists in Vaccines R&D and Al across Europe, US and Asia, holding Research Board, Innovation Board, Clinical Quality Board and Data Governance Board responsibilities.
Working across biological discovery, clinical development and public health, he discovered the pangenome concept co-founding the pangenomics discipline, contributed to the successful registration of four novel vaccines, including the first universal vaccine against serogroup B meningitis, led the Meningococcal Antigen Typing System (MATS) platform worldwide, developed transformative corporate data strategies, authored 70+ publications, books and patents in data science for health, population genomics and mathematical vaccinology.
Prof. Medini received his Ph.D. in Physics from the University of Perugia, Italy, with a residency at the Northeastern University in Boston, MA; is habilitated Full Professor of Molecular Biology; has served in international PhD school committees at the Perugia and Turin Universities in Italy; is honorary member of the Cuban Immunology Society, Fellow of the ISi Foundation, Board member of the WHO mRNA Hub program and of the New Zealand National RNA program, Steering Committee member of the Global Pandemic Prevention & Biodefense Center at Connected OMV; an IMO, ADVAC and UC Berkley
alumnus.
