The SDEE event on October 12, 2023, at Hera Hub was especially interesting and timely, as it focused on mRNA therapeutics. The speakers were Paul Daruwala, President and CEO of Cellics Therapeutics, Chunping Xu, Director of Chemistry at TriLink Biotechnologies/Maravai Lifesciences, and Jiwu Wang, President and CEO of Allele Biotech and member of SDEE’s Board of Directors.

mRNA became a household name in 2021 when BioNTech and Moderna launched COVID-19 vaccines just a year after the beginning of the pandemic, arguably saving millions of lives around the word. The record speed development of mRNA-based vaccines was possible thanks to years of behind-the-scenes research that in September was recognized with the award of the Nobel Prize in Physiology or Medicine to Katalin (Kati) Kariko’ and Drew Weissman.

Although vaccines were the first application of mRNA as a therapeutic agent, research in this field is active in the pursuit of other applications for mRNA, siRNA, lincRNA, saRNA, RNAi, and circRNA. Numerous companies work in this field, either developing therapeutic molecules or acting as contract development and manufacturing organizations (CDMO). In addition to Moderna, BioNTech, TriLink/Maravai, and Allele, the list includes GSK (Curavac), AstraZeneca (VaxEquity), Arcturus, Orna, Replicate Bioscience, Laronde, Alnylam, HAYA, Cargene/Lerna, Millipore/Sigma, Lonza, Samsung, and many others.

mRNA-based therapies do not raise the safety issues of DNA because they do not integrate in the genome. In addition, translation occurs rapidly in the cytoplasm. However, RNA-based therapeutics need to be stable, pure, have the appropriate potency, reach the appropriate tissue, and be incorporated into cells without generating an immune response.

TriLink/Maravai specializes in the chemical modifications of mRNA to increase stability and potency and decrease immunogenicity. They have devised several capping strategies that are easy and inexpensive to perform, while leading to low contamination with DNA and proteins, high yield and protein production, and low immunogenicity.

Delivery of RNA-based therapies can constitute another challenge. Cellular nanoparticles (CNP) developed by Cellics are nanoparticles coated with wild-type or engineered cell membranes from red blood cells or macrophages. They offer the potential to deliver mRNA, siRNA, and other molecules to the appropriate tissue upon intramuscular, intravenous, or inhalation route. Interestingly, CNP without payload can be used as nonosponges to remove bacterial toxins, viruses, or cytokines.

Photo: Jiwu Wang, President and CEO of Allele Biotech and member of SDEE Board of Directors

Allele specializes in mRNA transfection to make induced pluripotent stem cells (iPSC) after just a few days in culture. iPSC can differentiate into many different cell types, including pancreatic beta cells that have shown potent insulin production in animal models of diabetes.

SDEE wishes to thank the speakers, the attendees, the Hera Hub and all the sponsors: Morrison and Foerster, Alexandria, Kyowa Kirin, Takeda, CBRE, BDO, Marsh & McLennan, MUFG, Scientist.com, JLABS, College of International IP Rights, Duane Morris, and Longfellow.