Principal Entity:
5 Prime Sciences Inc
Project of $999,984 over 18 months
- Supported by CQDM through:
Ministère du Développement économique, de l’Innovation et de l’Énergie (MDEIE) - By co-funding partner:
– 5 Prime Sciences Inc.
The project in detail:
Challenge:
RNA-based therapeutics, including small interfering RNA (siRNA) and antisense oligonucleotides (ASOs), are transforming drug development by enabling durable, tissue-specific silencing of disease-causing genes. However, a major bottleneck remains the identification of suitable biological targets that causally drive human disease and are actionable for RNA modalities for RNA therapies. Existing target discovery approaches rarely account for RNA-specific requirements such as tissue-specific expression, exon-skipping or the inhibition-requiring direction of effect. As a result, the field lacks scalable computational platforms that systematically integrate human genetic evidence to prioritize RNA therapeutic targets leading to inefficient R&D investment and delayed access to effective medicines for patients.
Solution:
LOFTier is a proteogenomic target prioritization platform developed by 5 Prime Sciences to identify disease-causing genes that are suitable for RNA-based therapies. It integrates large-scale genomic, proteomics, expression, splicing, loss-of-function variants, and clinical outcome databases to identify genes that causally drive disease and to generate evidence-weighted target rankings using machine learning methods trained and validated on large human datasets. In this project, LOFTier will be applied and validated to prioritize targets for siRNA and ASO drug design across multiple high-burden disease areas including metabolic liver disease (MASLD/NASH), neurodegeneration, chronic kidney disease, and inflammatory conditions. Its high-throughput, multi-indication approach is intended to improve target selection.
Expected Achievements /Impacts:
LOFTier is expected to improve RNA therapeutic target selection by integrating human genetic, proteogenomic, and expression data into an RNA-specific prioritization framework. The platform should help identify targets that are more causally linked to disease, more tissue-specific, and better suited for siRNA, ASO, or exon-skipping approaches. By enabling scalable target prioritization across multiple high-burden disease areas, LOFTier could reduce inefficient R&D investments, support better early-stage decision-making, and decrease the risk of costly late-stage failures in RNA drug development. It may also strengthen 5 Prime Sciences’s commercial positioning by supporting partnerships with pharmaceutical and biotechnology companies active in RNA therapeutics. This project is important for Québec as it supports the growth of a local life sciences company in a strategic and rapidly expanding field, while reinforcing the province’s expertise in genomics, computational biology, and RNA therapeutic innovation.
