Lung adenocarcinoma (LUAD) is the greatest cancer killer in Ireland and worldwide. Prognosis remains poor, due to limited treatment options, drug resistance, and side effects.
Addressing the needs of patients, their families and carers for improved therapies is the aim of this Project. To do so, we propose a solution in the powerful new technology of RNA therapeutics (RNATx). RNATx is proven to deliver programmable, safe and effective control of disease gene expression in vivo, opening up an wide panorama of therapeutic targets and benefitting from a validated and streamlined pathway to the clinic. The promise of RNATx was recognised in 2023 with the Nobel Prize in Medicine.
Given its novelty, RNATx requires new targets. This Project takes advantage of newly discovered therapeutic targets from the Applicant Group. These targets come from the promising class of oncogenes, the long noncoding RNAs (lncRNAs), offering potent and personalised disease-modifying activity with reduced off-target toxicity. Inhibitory antisense oligonucleotide (ASO) drugs will be designed and validated against these targets. These ASOs will be aggressively filtered through a carefully-designed pipeline, comprising patient-derived disease models (efficacy), non-disease models (toxicity), and synergism with existing drugs (therapy resistance). Target validation will be guided by patient samples and data, and employs state-of-the-art models.
This will be achieved by a newly assembled, international collaborator team uniting world-leading expertise in RNATx, patient models and in vivo models. The relevance of our work will be monitored by a PPI Committee. The outcome will be thoroughly characterised anti-cancer RNATx molecules, ready for commercial investment and clinical development. Thus, this Project is carefully focussed to maximise benefit for LUAD patients by opening a new therapeutic front in oncology and propelling promising new therapies towards the clinic.