Why INT2ACT?
Chemical modifications on mRNA (specifically methylation) are instrumental in dictating mRNA fate in cells, e.g. stability, translational efficiency, intracellular localisation. Targeted manipulation of these modifications either in cells or on expression vectors has the potential to improve advanced therapy manufacturing efficiencies in various host cell types.
Prof. Niall Barron is a Principle Investigator at the National Institute for Bioprocessing Research and Training in Dublin, Ireland.
Biological medicines based on proteins, nucleic acids or even living cells are difficult to manufacture efficiently, safely and economically. Prof. Barron’s research group focuses on understanding and improving the cell systems used to create these therapies with a particular emphasis on the cellular molecular mechanisms involved. They apply advanced omics technologies in collaboration with Dr.Colin Clarke’s Bioinformatics group at NIBRT to identify the genes and pathways that contribute to cellular phenotypes relevant to, for example, producing monoclonal antibodies or other therapeutic proteins in Chinese Hamster Ovary (CHO) cells.
In this way they try to develop genetic engineering strategies to enhance the ability of the host cell line to make these products more efficiently. These strategies include manipulating the expression of specific endogenous genes (including non-coding RNAs, not just protein-encoding genes) in the host cell line, introducing exogenous sequences into the host or modifying the genome directly – ideally in a highly targeted manner.
They apply similar strategies to enhancing the manufacturing platforms for viral gene therapy vectors (e.g. AAV or lentivirus) including HEK293 or Sf9. Gene therapies present unique challenges in terms of their production including low yield, high variability and a dependency on large-scale transient transfection of multiple expression plasmids. Modified cell therapies (e.g. CAR-T) are another exciting new modality demonstrating some spectacular clinical results but which, particularly in the autologous setting, are exceptionally challenging to manufacture. They are interested is various aspects of creating these cell therapies including more efficient gene delivery approaches and the use of modified RNA to enhance the expression of the relevant transgenes.
I have always been fascinated by the idea of creating useful ‘products’ using biological systems, i.e. biotechnology. My early career focused on production of bioethanol from agricultural waste using fungal enzymes and genetically engineered yeast strains. Over the subsequent years my interests evolved towards applying various cell engineering approaches to the manufacture of biological therapies including recombinant proteins, viral gene therapy vectors and modified cell therapies.
I obtained a BA(Mod) in Microbiology from Trinity College Dublin and PhD in Applied Microbiology/Biochemistry from the University of Ulster in 1997. I spent three years at Baylor College of Medicine in Houston, Texas as a postdoctoral scientist working on genome engineering strategies to study nuclear steroid receptor function before returning to Ireland to work on stem cell engineering at the National Cell and Tissue Culture Centre in DCU. Subsequently, as a senior scientist in the National Institute for Cellular Biotechnology (NICB), I helped grow the mammalian cell engineering group with a specific focus on the production of recombinant therapeutic proteins. I was appointed Professor of Biochemical Engineering in the School of Chemical and Bioprocess Engineering in UCD and NIBRT Principal Investigator in 2017.
- Donohue N, Li S, Boi S, Rainbow-Fletcher A, Barron N. (2025). Production of an Oncolytic Adeno-Associated Virus Containing the Pro-Apoptotic TRAIL Gene Can Be Improved by shRNA Interference. Intl J Mol Sci 26 (2), 567.
- Hefzi, H., Martínez-Monge, I., Marin de Mas, I. et al. (2025). Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells. Nat Metab. 7(1):212-227. Barron N. is co-author. https://doi.org/10.1038/s42255-024-01193-7
- Tzani I, Castro-Rivadeneyra M, Kelly P, Strasser L, Zhang L, Clynes M, Karger BL, Barron N, Bones J, Clarke C. (2024). Detection of host cell microprotein impurities in antibody drug products. Nat Commun. 15(1):8605. doi: 10.1038/s41467-024-51870-0. PMID: 39366928; PMCID: PMC11452709.
- Foley A, Lao N, Clarke C, Barron N. (2024). A complete workflow for single cell mtDNAseq in CHO cells, from cell culture to bioinformatic analysis. Front Bioeng Biotechnol. 19;12:1304951. doi: 10.3389/fbioe.2024.1304951.
- Lao N, Barron N. (2023). Enhancing recombinant protein and viral vector production in mammalian cells by targeting the YTHDF readers of N6 -methyladenosine in mRNA. Biotechnol J. Apr;18(4):e2200451. doi: 10.1002/biot.202200451