Translational Impact Research

The Translational Impact Research (TIR) funding program supports large-scale translational research projects in RNA-based therapeutics, which address D2R’s strategic priorities, and have a measurable translational impact on the health of Canadians.

In the first funding cycle launched in 2024, 11 Letters of Intent were received of which four were invited to submit full applications. Three full applications were received and awarded. View a summary of the review and selection process.

Funded project summaries

RNA therapy for a severe and ultra-rare disease

Schinzel-Giedion Syndrome is a devastating and rare genetic disease leading to neurological deterioration and Cystic Fibrosis-like lung disease. Most people with SGS die in the first decade of life and there is no treatment that targets the underlying cause of disease. SGS is caused by missense mutations in the SETBP1 gene which result in an accumulation of the SETBP1 protein. By reducing the level of SETBP1 mRNA, SETBP1 protein levels can be decreased offering a potential treatment for SGS. Using antisense oligonucleotides (ASO), we have successfully reduced SETBP1 protein levels in SGS patient derived progenitor brain cells and SGS mouse disease models. The purpose of this grant is to manufacture and test an RNA therapy for SGS and use it to reduce seizure burden in one SGS individual. We will use a unique clinical trial mechanism in Canada, the Single Patient Clinical Trial. We hope to reduce suffering in the daily life of children suffering from SGS.

Principal investigator: Carl Ernst (McGill University)

Co-investigators : Larry Lands (MUHC), Darcy Wagner (MUHC), Keith Murai (MGH), Ken Myers (MCH), Ziv Gan-Or (MNI), Sebastian Jacquemont (St Justine), Raluca Pana (MNI), Alexander Weil (St Justine), Karl Muchantef (MCH)

Award duration: 3 years

Relevant D2R axes: RNA Therapeutics (Axis 2) Clinical Research, Acceleration, and Implementation (Axis 4) , Population Studies and Genomic Medicine (Axis 1)

Innovative RNA therapies offer new hope for patients affected by POLR3-related leukodystrophy

Leukodystrophies are rare genetic brain disorders affecting previously healthy children. POLR3-related hypomyelinating leukodystrophy (POLR3-HLD) is characterized by reduced white matter (myelin) production in the brain. It results from mutations in genes that code for RNA polymerase III (Pol III), an essential complex for producing RNA, including transfer RNAs (tRNAs) necessary for protein production. This project aims to develop RNA-based treatments for POLR3-HLD through three strategies: first, using antisense oligonucleotides (ASOs) to target and modify the disease-causing genetic message in affected patients; second, restoring POLR3A function (a critical Pol III subunit) by delivering healthy mRNA via lipid nanoparticles (LNPs); and finally, we are exploring an ASO approach to reduce MAF1, a Pol III inhibitor, to enhance its activity. These therapies will be preclinically tested in cell and mouse models to ensure safety and efficacy, with patient, organization, and industry support to ensure rapid transition to clinical trial.

Principal investigator: Geneviève Bernard (Research Institute of the McGill University Health Centre)

Co-investigators: Thomas Durcan (McGill University), Timothy Kennedy (McGill University), McGill University), Philippe Huot (McGill University)

Collaborators: Guillaume Bourque (McGill University), Masad Damha (McGill University), Pieter Cullis (University of British Columbia), Ian Willis, (Albert Einstein College of Medicine), Austen Milnerwood (McGill University), Nahum Sonenberg (McGill University), François-Xavier Lacasse (Université de Montréal)

Partnering organizations : Jude Tallman and Family, Fondation Les Amis d'Elliot, Leuco Action, Yaya Foundation for 4H Leukodystrophy, Montreal Children's Hospital Foundation, RI-MUHC, Early Drug Discovery Unit (McGill), NanoCore, C3G Platform, Andor Technology, Dendrotek Biosciences, Parse Biosciences, RNA technologies & Therapeutics Inc.

Award duration: 3 years

Relevant D2R axes: RNA Therapeutics (Axis 2) Clinical Research, Acceleration, and Implementation (Axis 4) , Data Science, Bioinformatics, and Computing in Personalized Medicine (Axis 5)

The Jerry Pelletier initiative: Diagnostic and therapeutic innovations for rare cancers

Despite great advances overall in cancer therapy, patients with rare subtypes of tumours do not benefit adequately from personalised treatments due to the lack of basic knowledge of the underlying biological factors that drive these cancers. Since these patients often do not respond to standard-of-care approaches and then become resistant to therapies currently available, physicians at present have limited treatment options. We are undertaking a coordinated multi-disciplinary program that will use advanced genomics to identify the most viable biomarkers and likely therapeutic targets for patients with rare types of tumours and then exploit this knowledge to obtain RNA-based and other treatments adapted to each patient. Furthermore, our comprehensive genomic studies and tumour modeling of rare cancer subtypes will generate resources that can be used by the research community to identify new ways to tackle these difficult-to-treat malignancies.

Principal investigator: Mark Lathrop (McGill University), Morag Park (McGill University)

Co-investigators: Gerald Batist (McGill University), Guillaume Bourque (McGill University), Thomas Duchaine, (McGill University), William Foulkes (McGill University), Livia Garzia (McGill University), Sidong Huang (McGill University), Nada Jabado (McGill University), Mark Lathrop (McGill University), Morag Park (McGill University), Ioannis Ragoussis (McGill University), Yasser Riazalhosseini (McGill University), Ramy Saleh (McGill University)

Collaborators: Mark Basik (McGill University), Mathieu Blanchette (McGill University), Julia Burnier (McGill University), Guojun Chen (McGill University), David Juncker (McGill University), Wassim Kassouf (McGill University), Claudia Kleinman (McGill University), Sampath Loganathan (McGill University), Raquel Cuella Martin (McGill University), Heather Melichar (McGill University), William Muller (McGill University), Peter Siegel (McGill University), Hanadi Sleiman (McGill University), Nahum Sonnenberg (McGill University), Simon Tanguay (McGill University), Ian Watson (McGill University)

Post-doctoral fellows: Rocio Conforti Ayelem (McGill University), Zohreh Mehrjoo (McGill University), Monica Lara Marquez (McGill University), Behrang Sharif (McGill University)

Partnering organizations: Oxford Nanopore Technologies, 10x Genomics

Award duration: 3 years

Relevant D2R axes: Population Studies and Genomic Medicine (Axis 1) RNA Therapeutics (Axis 2) , Clinical Research, Acceleration, and Implementation (Axis 4)