Pre-clinical evaluation of Moderna LNP-mRNA therapy for citrin deficiency
The Foundation is sponsoring a joint research collaboration between Moderna Therapeutics, the University of Cambridge, UK (Prof. Edmund Kunji), and the University of Melbourne, Australia (A/Prof. Diana Stojanovski), to conduct in vitro pre-clinical studies on the therapeutic potential of Moderna’s lipid nanoparticle (LNP)-mRNA encoding wild type citrin for citrin deficiency (CD).
The LNP-mRNA constructs utilized in this collaborative effort are improved versions previously employed and reported by Cao et al. 2019, Molecular Therapy.
The planned studies will investigate important aspects such as the biogenesis of mRNA-derived citrin protein and its import into the mitochondria to its subcellular localization. It will also study the protein half-life of translated citrin protein, assess citrin protein expression levels, and determine whether the LNP-mRNA constructs can restore bioenergetic profiles and rescue affected metabolic pathways in citrin knock-out and citrin mutant knock-in cell lines.
We expect the findings from this joint collaboration to lay the foundations towards pre-clinical in vivo studies using LNP-mRNA therapies for CD.
(Updated January 2024)
Professor Edmund Kunji holds a PhD in Mathematics and Natural Sciences from the University of Groningen, The Netherlands. He carried out his post-doctoral studies in the group of Dr Richard Henderson at the MRC Laboratory of Molecular Biology, Cambridge. Since 2000, he is a programme leader at the MRC Mitochondrial Biology Unit, University of Cambridge, where he works with his team on the role of mitochondrial transport proteins in the translocation of metabolites, cofactors and inorganic ions across the mitochondrial inner membrane. Since 2019, he is Professor of Biophysics in Clinical Neurosciences of the University of Cambridge.
Dr Diana Stojanovski is a mitochondrial biologist located in the Department of Biochemistry and Pharmacology at the University of Melbourne and the Bio21 Institute. Dr Stojanovski obtained her PhD from La Trobe University in 2006 where she worked with Prof. Mike Ryan on the emerging topic of mitochondrial dynamics. In 2006, she moved to the University of Freiburg as an Alexander von Humboldt research fellow working with Prof. Nikolaus Pfanner on protein translocation systems in yeast mitochondria. Diana returned to La Trobe University in 2009 as an Australian post-doctoral fellow and in 2013 she was recruited to the University of Melbourne to start her independent research group.