Synthetic mRNAs Containing Minimalistic Untranslated Regions Are Highly Functional In Vitro and In Vivo
Shahab Mamaghani,
Rocco Roberto Penna,
Julia Frei,
Conrad Wyss,
Mark Mellett,
Thomas Look,
Tobias Weiss,
Emmanuella Guenova,
Thomas M. Kündig,
Severin Lauchli,
Steve Pascolo
Affiliations
Shahab Mamaghani
Department of Dermatology, University Hospital Zurich (USZ), University of Zurich (UZH), Raemistrasse 100, 8091 Zurich, Switzerland
Rocco Roberto Penna
Department of Dermatology, University Hospital Zurich (USZ), University of Zurich (UZH), Raemistrasse 100, 8091 Zurich, Switzerland
Julia Frei
Department of Dermatology, University Hospital Zurich (USZ), University of Zurich (UZH), Raemistrasse 100, 8091 Zurich, Switzerland
Conrad Wyss
Department of Dermatology, University Hospital Zurich (USZ), University of Zurich (UZH), Raemistrasse 100, 8091 Zurich, Switzerland
Mark Mellett
Department of Dermatology, University Hospital Zurich (USZ), University of Zurich (UZH), Raemistrasse 100, 8091 Zurich, Switzerland
Thomas Look
Department of Dermatology, University Hospital Zurich (USZ), University of Zurich (UZH), Raemistrasse 100, 8091 Zurich, Switzerland
Tobias Weiss
Department of Neurology, Clinical Neuroscience Center, University Hospital Zurich (USZ), University of Zurich (UZH), Frauenklinikstrasse 26, 8091 Zurich, Switzerland
Emmanuella Guenova
Lausanne University Hospital (CHUV), University of Lausanne, 1015 Lausanne, Switzerland
Thomas M. Kündig
Department of Dermatology, University Hospital Zurich (USZ), University of Zurich (UZH), Raemistrasse 100, 8091 Zurich, Switzerland
Severin Lauchli
Department of Dermatology, University Hospital Zurich (USZ), University of Zurich (UZH), Raemistrasse 100, 8091 Zurich, Switzerland
Steve Pascolo
Department of Dermatology, University Hospital Zurich (USZ), University of Zurich (UZH), Raemistrasse 100, 8091 Zurich, Switzerland
Synthetic mRNA produced by in vitro transcription (ivt mRNA) is the active pharmaceutical ingredient of approved anti-COVID-19 vaccines and of many drugs under development. Such synthetic mRNA typically contains several hundred bases of non-coding “untranslated” regions (UTRs) that are involved in the stabilization and translation of the mRNA. However, UTRs are often complex structures, which may complicate the entire production process. To eliminate this obstacle, we managed to reduce the total amount of nucleotides in the UTRs to only four bases. In this way, we generate minimal ivt mRNA (“minRNA”), which is less complex than the usual optimized ivt mRNAs that are contained, for example, in approved vaccines. We have compared the efficacy of minRNA to common augmented mRNAs (with UTRs of globin genes or those included in licensed vaccines) in vivo and in vitro and could demonstrate equivalent functionalities. Our minimal mRNA design will facilitate the further development and implementation of ivt mRNA-based vaccines and therapies.
