The Foundational Projects funding program supports high-risk, early-stage projects with the potential to be game-changers in the fields of D2R’s areas of interest.
In the second funding cycle launched in 2025, 46 applications were received of which 23 received awards. View a summary of the review and selection process.
Funded project summaries
RNA-based therapeutic with enhanced mechanisms of action for telomerase inhibition in cancer
Telomerase is an enzyme consisting of RNA and protein that plays a role in stabilizing the ends of chromosomes. Telomerase is present in 85% of cancer cells but rarely in normal cells and is a potential anticancer target. Despite 30 years of research, only one drug against telomerase has been approved by the federal drug agency for one specific indication, requiring a high dose causing significant side effects and thus having limited use. We will identify and optimize two RNA therapeutics in vitro and in cells to target two regions of telomerase essential for its function.
Principal Investigator: Chantal Autexier (Jewish General Hospital)
Co-Investigator(s): N/A
Collaborator(s): George Kukolj (McGill University)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
A RNA-based approach to selectively inhibit the RNA master transcription factor NRF2
Lung cancer accounts for 12.3% of all new cases diagnosed in 2023, making it the second most frequent cancer globally. Although early-stage lung tumors are increasingly curable, most of them become resistant to various anticancer treatments, which results in treatment failure. Our innovative approach capitalizes on KEAP1 protein alterations that provide resistance to a range of anticancer treatments. We are creating medications that aid tumors in overcoming therapy resistance. Additionally, normal cells that do not contain these mutations are unaffected by them. This is a potential transformational approach that might improve and extend the efficacy of several anticancer treatments.
Principal Investigator: Gerald Batist (Jewish General Hospital)
Co-Investigator(s): Jian Hui Wu (McGill University)
Collaborator(s): N/A
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
Polyvalent circular RNA vaccine and recombinant vaccine production
As new viruses emerge, infectious disease researchers need to test RNA vaccines’ effectiveness using pre-clinical animal models first. However, manufacturing and testing RNA vaccines against new pathogens or each new variant can be difficult for many researchers. Here, we propose to create a technique that can generate circular RNA vaccines for up to 12 different virus antigens and variants simultaneously in insect cells all in a single DNA plasmid. Insect cell culture is cheap and easy to work with, and facilities exist worldwide. Our project will lower the barrier for researchers to generate circular RNA vaccines for multiple antigen variants.
Principal Investigator: Brian Chen (Research Institute of the McGill University Health Centre)
Co-Investigator(s): N/A
Collaborator(s): N/A
Project duration: Two-year
D2R Axes: RNA Therapeutics (Axis 2)
Dissecting and Targeting the Cellular Drivers of Edema in Brain Cancer
Glioblastoma is an aggressive brain cancer often complicated by swelling in the brain, known as edema, which worsens symptoms and limits treatment. Current drugs to reduce swelling weaken the immune system, worsening immunotherapy response. This project will combine brain imaging with advanced techniques that measure gene activity in brain tumors to understand what causes this swelling. We will then test new treatments—including RNA-based therapies—that aim to reduce swelling without weakening the immune response. This research could lead to better, safer treatments by directly targeting one of the most harmful and poorly understood features of brain cancer.
Principal Investigator: Charles Couturier (McGill University)
Co-Investigator(s): N/A
Collaborator(s): Louis Collins (Montreal Neurological Institute-Hospital), Daniela Quail (Goodman Cancer Institute)
Project duration: Two-year
D2R Axes: Data Science, Bioinformatics, and Computing in Personalized Medicine (A5)
A twist in the tail: optimizing mRNA termini for enhanced protein production
Messenger RNA (mRNA) medicines have the potential to treat a wide range of diseases, including genetic disorders, cancer and infectious disease. However, the underlying technology is still in its infancy. Importantly, of the many design considerations, mRNA stability is critical for therapeutic protein production. Yet, current designs have not incorporated elements to actively stabilize mRNA medicines. As such, the goal of this study is to identify strategies that improve mRNA stability for the development of more potent mRNA vaccines and therapeutics.
Principal Investigator: Marc Fabian (Jewish General Hospital)
Co-Investigator(s): Selena Sagan (University of British Columbia), Eric Jan (University of British Columbia)
Collaborator(s): Sarah Hedtrich (University of British Columbia)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
KIDNET: Kidney-Intelligent Delivery via Nano-Encapsulation and Targeting
We are developing a new technology to safely deliver RNA-based treatments to the kidney. These treatments could help people with rare genetic kidney diseases by correcting the root cause at a molecular level. Our team uses lipid nanoparticles (LNPs), which carry RNA into specific kidney cells. By attaching molecules to these LNPs we aim to guide them to the target cells in the kidney, making RNA therapies more precise and effective. This research could lead to new treatments for currently untreatable kidney diseases and help accelerate the creation of new therapies.
Principal Investigator: Paul Goodyer (Research Institute of the McGill University Health Centre)
Co-Investigator(s): Christopher Moraes (McGill University)
Collaborator(s): Elena Torban (McGill University)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
Investigate a novel small RNA-directed mechanism driving HIV latency and beyond
We aim at providing a novel solution to HIV cure through investigating a mechanism that cells have evolved to suppress the activity of abundant retroviral DNA in human genome. We will demonstrate that as a retrovirus, HIV is subject to the control of this mechanism and is consequently driven into latency. The key effector of this mechanism is tRNA-derived fragments that target viral primer binding site which is copied from tRNA and is used by all retroviruses. Selectively blocking this mechanism with antisense oligonucleotides is expected to disrupt HIV latency and promote immune clearance of HIV reservoir cells.
Principal Investigator: Chen Liang (Jewish General Hospital)
Co-Investigator(s): N/A
Collaborator(s): N/A
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
Harnessing the vaccine potential of Schistosoma mansoni cercariae
Schistosomiasis is a parasitic disease that affects over 250 million people and causes major losses in agriculture. Current treatment does not prevent reinfection, and no vaccine exists for humans or animals. Previous studies have shown that weakened form of the parasite's larval stage offers strong protection, but it is not safe for human use. This project will study how these larvae trigger immunity by analyzing their surface proteins and sugars. We will also test how the immune system responds and identify promising vaccine targets. The goal is to develop a new, long-lasting vaccine to protect both people and animals.
Principal Investigator: Thavy Long (McGill University)
Co-Investigator(s): Momar Ndao (McGill University)
Collaborator(s): Jeff Xia (McGill University), Lara Mahal (University of Alberta)
Project duration: Two-year
D2R Axes: Data Science, Bioinformatics, and Computing in Personalized Medicine (A5)
Early assessment of the value of novel RNA therapeutics in genomic newborn screening initiatives: health, economic and ethical implications
New programs are beginning to screen newborns for many rare diseases using advanced genetic tools. This kind of testing is likely to become more common over the next 10–20 years. But in many cases, there are no treatments yet for the conditions being tested. Our project explores how new RNA-based therapies could help treat these diseases. We will build tools and a public database to help researchers decide which conditions to focus on first. This work will also guide future health programs and policies, with special attention to improving access and fairness for underserved communities and families.
Principal Investigator: Larry Lynd (University of British Columbia)
Co-Investigator(s): Ma'n Zawati, (McGill University), Yann Joly (McGill University)
Collaborator(s): Mark Harrison (University of British Columbia), Carl Ernst (McGill University), Paul Goodyer (McGill University)
Project duration: Two-year
D2R Axes: Ethical, Socioeconomic, and Cultural Dimensions in Genomic Research (A6)
Targeting miRNAs in Embryonal Brain Tumors
Embryonal Tumors with Multilayered Rosettes (ETMR) are rare and aggressive paediatric brain tumors. They occur predominantly in children under the age of three, are incurable, and the post-diagnosis survival time is approximately 12 months. ETMRs are caused by a genome rearrangement resulting in high level of expression of small regulatory RNAs (microRNAs). In this project we will study the molecular effects of this genome rearrangement and explore the use of microRNA inhibitors – sponges – to counteract the oncogenic changes. Ou research has the potential to identify therapeutic approaches for treating this deadly and devastating tumor.
Principal Investigator: Jacek Majewski (McGill University)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
Switchable self-amplifying RNA: Safe, Selective, and Programmable Therapeutic Expression
Self-amplifying RNA (saRNA) is a promising new drug type for treating disease, but once inside the body, it’s difficult to control. Our goal is to create “smart” RNA molecules that can turn on, turn off, or fine-tune their activity in response to cues inside specific cells. By embedding tiny self-cleaving switches (called ribozymes) into the RNA, we can design therapies that are safer, more targeted, and more adaptable. These new RNA tools are built entirely from chemical components, require no added proteins, and could help pave the way for next-generation treatments in cancer, immune disorders, and rare diseases.
Principal Investigator: Maureen McKeague (McGill University)
Collaborator(s): Anna Blakney (University of British Columbia)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
Engineering a Novel Type of Liposomal Nanoparticles for BIRC5 Gene Silencing and Therapeutical Evaluation in Colon Cancer
Colorectal cancer is a deadly disease, especially when it spreads. Some cases resist treatment due to TP53 gene mutations , which leads to increase production a BIRC5 protein also called survivin, helping cancer cells to survive. To tackle this, we plan to shut down the BIRC5(survivin) gene using gene silencers packaged into a new type of tiny fat-based carriers. We will test this method alongside CuET, a drug derived from an FDA-approved medication, and standard chemotherapy that previously to control failed due to resistance. The goal is to make the cancer vulnerable again, improving treatment success and saving lives.
Principal Investigator: Danuta Radziach (Research Institute of the McGill University Health Centre)
Co-Investigator(s): Maryam Tabrizian (McGill University), Jonathan Cools (McGill University)
Collaborator(s): Marian Hajduch (Institute of Molecular and Translational MediciTra)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
Directing the delivery of RNA cargo to specific tissue targets using components derived from regulated exosome trafficking
Using the same kind of strategy that was employed for the mRNA vaccines during the pandemic, we should also be capable of using mRNAs to correct cellular deficiencies by introducing an mRNA that could provide a missing or faulty protein in patients. This strategy has not met the same success as the vaccines, since most of the RNA doesn't get to the target and when it does it gets sent to the cellular trash can. Our work focuses on improving the targeting of mRNAs and to persuade the cell into keep the mRNA medicine to improve patient health.
Principal Investigator: Richard Roy (McGill University)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
An innovative one-pot platform for high-throughput molecular interaction screening
This project aims to develop innovative technology to rapidly test thousands of molecular interactions in a single, streamlined experiment. The platform enables efficient, high-throughput screening by tagging molecules with unique DNA barcodes and organizing them on a chip. Initially applied to RNA and proteins, it can be adapted to study various molecular interactions. This approach could accelerate the discovery of new RNA-based therapies and diagnostic tools, providing a faster and more cost-effective method to understand complex biological systems and develop treatments for various diseases.
Principal Investigator: Reza Salavati (McGill University)
Collaborator(s): Hanadi Sleiman (McGill University)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
Targeting nuclear localization of IL33 to orchestrate a glioma inhibitory microenvironment
Glioblastoma is a fatal brain cancer with very few examples of long-term survivors. Therapies have focused on killing tumor cells, yet these have provided minimal clinical benefit. We believe that cells within the brain where the tumor resides contributes to tumor progression and therapeutic resistance. In the case of glioblastoma it is often filled with innate immune cells called macrophages/microglia and the tumor cells hijack them to fuel tumor progression. We have discovered that glioma cells that are highly infiltrated with macrophages express a molecule called IL33 that can control glioma growth and prolong overall survival.
Principal Investigator: Donna Senger (Jewish General Hospital)
Co-Investigator(s): Benjamin Martin (McGill University), Stephen Robbins (McGill University)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
Accelerating design of RNA aptamer-based therapeutics with computer modeling
This project aims to speed up the discovery of RNA aptamers—short RNA molecules that can bind to disease-related targets and act as therapeutics. Using computer simulations and machine learning, we will predict which RNA sequences are most likely to bind effectively to small molecules of interest. By combining these predictions with laboratory experiments, we can find new aptamers faster and more efficiently. The long-term goal is to build a platform that helps design RNA-based drugs with improved precision, making it easier to develop treatments for conditions that are currently hard to target with existing therapeutics.
Principal Investigator: Lena Simine (McGill University)
Collaborator(s): Maureen McKeague (McGill University)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
Rational design of optimized IRESes for therapeutic circular RNAs
Messenger RNA therapies have shown great promise, especially in COVID-19 vaccines, and efforts are underway to expand their use for diseases like cancer, autoimmune disorders, and genetic conditions. A key challenge is ensuring these treatments produce sufficient protein over an extended period. Recent advancements in circular RNA (circRNA) show that its closed-loop structure enhances stability and protein production. We aim to engineer internal ribosome entry site elements from the protein ITAF45 to develop programmable circRNAs that can "turn on" protein production in specific disease conditions, offering targeted RNA-based treatments that minimize side effects and enhance effectiveness.
Principal Investigator: Nahum Sonenberg (McGill University)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
DDX3X/Y and mRNA Translation in Melanoma
Melanoma exhibits sex-based differences, with higher incidence and worse prognosis in males compared to females. The DDX3X and DDX3Y genes, located on the X and Y chromosomes, encode RNA helicases involved in transcription, translation, and cell cycle regulation. DDX3X exhibits a sex-specific tumor suppressor role in male melanomas, where it is often mutated. In one-fourth of male melanomas, DDX3Y is not expressed because of the loss of the Y chromosome. Our research exploring the roles of DDX3X and DDX3Y in the translational control of target mRNAs could shed light on sex-specific melanoma mechanisms and reveal therapeutic opportunities.
Principal Investigator: Nahum Sonenberg (McGill University)
Co-Investigator(s): Ian Watson (McGill University)
Collaborator(s): Joaquin Ortega (McGill University), Pavel Baranov (University College Cork)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
Designing RNA reporters to identify and eradicate metastatic cancer cells
During cancer progression, tumor cells acquire the ability to spread from primary lesions and grow secondary tumors in distant organs that are called metastases. Metastases are a major cause of cancer-related deaths. The mechanisms underpinning metastasis remain obscure thus impeding the efforts to prevent and/or treat metastatic disease. We recently discovered that specific changes in protein synthesis may distinguish early metastatic from non-metastatic cells. Herein, we propose to take advantage of these findings and generate RNA-based reporters that can be used to identify metastatic cells in the early stages of metastasis and eventually eradicate them.
Principal Investigator: Ivan Topisirovic (McGill University)
Co-Investigator(s): Josie Ursini-Siegel (McGill University)
Collaborator(s): Ola Larsson (Karolinska Institutet)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
mRNA-based intracellular immunotherapy: Bidirectional Control of Immune Signalling via TC-PTP-Targeting scFvs
Lipodystrophy is a rare disorder in which subcutaneous fat storage is severely limited. Without this “safe” fat storage, lipid spillover occurs, leading to profound insulin resistance—cells do not respond properly to insulin, causing elevated glucose and increasing the risk of cardiometabolic diseases. Notably, a milder “lipodystrophy-like” insulin resistance is common in the general population. This project will build AdipoSpliceAtlas—the largest catalog of gene-splicing variants in subcutaneous adipose tissue—to uncover how abnormal splicing contributes to lipodystrophy and its related disease spectrum. It will identify metabolically harmful splicing variants and lay the foundation for first-in-class splice-switching RNA therapeutics.
Principal Investigator: Michael L. Tremblay (McGill University)
Collaborator(s): Diane Sautter (McGill University)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
Small-Scale Mutation Repair in Primary Ciliary Dyskinesia using mRNA Therapeutics
Over the past 30 years, our study on TC-PTP gene (or PTPN2) has consistently demonstrated that it plays a crucial role in downregulating the immune system. While its inhibition can enhance anti-tumour responses, its activation may suppress excessive inflammation. This project develops engineered antibody fragments that selectively inhibit or activate TC-PTP within cells. They will be delivered as mRNA using lipid nanoparticles, allowing precise control of immune signalling. In preclinical models, inhibitory antibodies will be tested for cancer immunotherapy, while activators will be evaluated in colitis. This approach establishes a novel platform for mRNA-based intracellular immunotherapies that target immune regulation.
Principal Investigator: Caroline Wagner (McGill University)
Co-Investigator(s): Khanh Huy Bui (McGill University), Larry Lands (McGill University), Adam Shapiro (McGill University), Darcy Wagner (McGill University)
Collaborator(s): Sharon Dell (University of British Columbia), Guojun Chen (McGill University)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
Targeting XRP1 in ovarian cancer using small interfering RNAs
The standard of care for most ovarian cancers has not changed significantly in decades due to a lack of novel, effective therapeutic options. Recently, a protein target for ovarian cancers, termed XPR1, has been identified by multiple labs. Removing this target from ovarian tumors holds tremendous promise as a new therapeutic approach to treat these deadly cancers. We aim to develop a novel therapeutic to remove XPR1 from ovarian tumors. We also aim to deliver this therapy using innovative technology consisting of microscopic capsules. The successful completion of this project may reveal a novel therapeutic for a poor prognosis cancer.
Principal Investigator: Michael Witcher (Jewish General Hospital)
Collaborator(s): Maryam Tabrizian (Duff Medical Building), Marc Fabian (LDI/JGH)
Project duration: Two-year
D2R Axes: RNA Therapeutics (A2)
AdipoSpliceAtlas: Mapping Adipose Splicing Variants Driving Lipodystrophy and Lipodystrophy-Like Insulin Resistance.
Lipodystrophy is a rare disorder in which subcutaneous fat storage is severely limited. Without this “safe” fat storage, lipid spillover occurs, leading to profound insulin resistance—cells do not respond properly to insulin, causing elevated glucose and increasing the risk of cardiometabolic diseases. Notably, a milder “lipodystrophy-like” insulin resistance is common in the general population. This project will build AdipoSpliceAtlas—the largest catalog of gene-splicing variants in subcutaneous adipose tissue—to uncover how abnormal splicing contributes to lipodystrophy and its related disease spectrum. It will identify metabolically harmful splicing variants and lay the foundation for first-in-class splice-switching RNA therapeutics.
Principal Investigator: Satoshi Yoshiji (McGill University)
Collaborator(s): Josée Dupuis (McGill University), Vincent Mooser (McGill University)
Project duration: Two-year
D2R Axes: Population Studies and Genomic Medicine (A1)
