Dr Ingmar Hoerr, co-founder CureVac
Professor Katalin Karikó, University of Pennsylvania and BioNTech
The existence of mRNA was hypothesized early in the days of DNA breakthroughs in the 1960s. Research from the 1990s started to reveal its potential as a therapeutic tool, making use of its ability to create a specific protein, which then could act as a vaccine or to enable cell differentiation. This building pipeline for many different proteins creates the potential for diverse medical applications.
Researchers across the world were involved, with two notable European contributors into the scientific base upon which we now see mRNA therapies emerging.
Ingmar Hoerr was one such researcher in this field, with a PhD thesis in 2000 from the University of Tübingen entitled ‘RNA vaccine for the induction of specific cytotoxic T-lymphocytes (CTL) and antibodies’. He presented research that the fragile and short lived mRNA could be stabilised, creating an opportunity to explore its potential as a therapeutic intervention. His research showed that stabilised mRNA could stimulate the immune system and in 1999, he applied for his first patent, before founding CureVac in 2000, alongside colleagues from his laboratory.
After an early research career in mRNA through the 1990s, Hungarian researcher Karolin Karikó, working in the US at the University of Pennsylvania, determined how a reduced immune response could be created to mRNA, resulting from nucleoside modifications. Work was undertaken with Drew Weissman and published in articles from 2005, with the pair also holding associated patents granted from 2006 for non-immunogenic mRNA.
The road to commercial development with mRNA
Both Hoerr and Karikó followed their scientific discoveries into a commercial pathway. Hoerr was a co-founder of CureVac, whilst Karikó founded a small US company but subsequently followed her mRNA patents through to BioNTech after the IP was licensed to several other companies, including Moderna.
The role of mRNA in Covid vaccines crystallised only following the emergence of the pandemic, however clinical development for other applications was already underway for this novel class of drugs long before 2020. Diseases being targeted through companies active in mRNA include:
Cancer: Clinical trials are underway in prostate, melanoma, colorectal, head and neck, ovarian, pancreatic and multiple types of solid tumour.
Infectious disease: Covid-19 (See entry here), seasonal influenza, Zika virus and rabies, with pre-clinical work progressing in malaria, lassa/yellow fever, HIV, Epstein-Barr and tuberculosis.
The world can expect many more diseases to come into the spotlight of mRNA as scientific knowledge progresses, with the visibility of its role in Cobid-19 as a vital catalyst for global investment and attention.