mRNA-LNP Research Group

Research                                  

The information required for protein production is transmitted from the genetic material of cells to the site of protein synthesis by messenger molecules. Since the discovery of messenger RNA (mRNA), researchers have considered whether cells could be directed to produce specific proteins by delivering in vitro–produced mRNA molecules, thereby enabling protein expression without altering the cellular genome. Early studies demonstrated that this approach faced significant limitations. Exogenously delivered mRNAs frequently triggered undesirable innate immune responses and were rapidly degraded within cells. A breakthrough—recognized by the 2023 Nobel Prize—showed that the incorporation of modified nucleosides into mRNA molecules can substantially reduce these immune responses and improve the stability and translational efficiency of mRNA. The broad biotechnological and therapeutic potential of nucleoside-modified mRNA became achievable with the development of highly efficient delivery systems based on lipid nanoparticles (LNPs). The integration of nucleoside-modified mRNA with lipid nanoparticle technology has led to the emergence of the mRNA–LNP platform, which enables the transient production of specific proteins in cells without modifying their genetic material. This platform provides the foundation for a wide range of biomedical applications, including vaccine development, therapeutic protein delivery, and the development of anticancer vaccines. The objective of the mRNA–LNP Laboratory is to further advance this technology and facilitate its broad application. Our laboratory currently possesses the capability to routinely produce mRNA–LNP–based vaccines for preclinical studies in compliance with GLP quality standards. Our research group has participated in several major development programmes, including the development of lyophilisation procedures for mRNA–LNP formulations, the design and patenting of a novel lipid family suitable for LNP formation, and the development of vaccine candidates targeting viruses, bacteria, and pathogenic unicellular organisms. Our current research includes the development of mRNA-based therapeutic approaches aimed at overcoming resistance to anticancer chemotherapy and modulating tumour metabolism. In addition, we are involved in a program focused on the development of personalised cancer vaccines.

Group leader: Miklós Erdélyi scientific adviser

Group members: Csaba Bajusz research associate

Boglárka Takácsné Mihalik administrator expert

Publications:

 mRNA-LNP vaccine-induced CD8⁺ T cells protect mice from lethal SARS-CoV-2 infection in the absence of specific antibodies.

Montoya B, Melo-Silva CR, Tang L, Kafle S, Lidskiy P, Bajusz C, Vadovics M, Muramatsu H, Abraham E, Lipinszki Z, Chatterjee D, Scher G, Benitez J, Sung MMH, Tam YK, Catanzaro NJ, Schäfer A, Andino R, Baric RS, Martinez DR, Pardi N, Sigal LJ. Mol Ther. 2024 Jun 5;32(6):1790-1804. doi: 10.1016/j.ymthe.2024.04.019. Epub 2024 Apr 11.

Expression and purification of the receptor-binding domain of SARS-CoV-2 spike protein in mammalian cells for immunological assays.

Ábrahám E, Bajusz C, Marton A, Borics A, Mdluli T, Pardi N, Lipinszki Z. FEBS Open Bio. 2024 Mar;14(3):380-389. doi: 10.1002/2211-5463.13754. Epub 2024 Jan 24.

Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses.

McMahon M, O'Dell G, Tan J, Sárközy A, Vadovics M, Carreño JM, Puente-Massaguer E, Muramatsu H, Bajusz C, Rijnink W, Beattie M, Tam YK, Kirkpatrick Roubidoux E, Francisco I, Strohmeier S, Kanekiyo M, Graham BS, Krammer F, Pardi N. Proc Natl Acad Sci U S A. 2022 Nov 8;119(45):e2206333119. doi: 10.1073/pnas.2206333119. Epub 2022 Nov 2.

Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses.

Pardi N, Carreño JM, O'Dell G, Tan J, Bajusz C, Muramatsu H, Rijnink W, Strohmeier S, Loganathan M, Bielak D, Sung MMH, Tam YK, Krammer F, McMahon M. Nat Commun. 2022 Aug 9;13(1):4677. doi: 10.1038/s41467-022-32149-8.

Lyophilization provides long-term stability for a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine.

Muramatsu H, Lam K, Bajusz C, Laczkó D, Karikó K, Schreiner P, Martin A, Lutwyche P, Heyes J, Pardi N. Mol Ther. 2022 May 4;30(5):1941-1951. doi: 10.1016/j.ymthe.2022.02.001. Epub 2022 Feb 4.