GET VALIDATION: GEne Therapy - VALidation of Individualized Dose, Auto-immunity and Therapeutic effect wIth OligoNucleotides

In this project we aim to prove that messenger RNA can be used as a safe and powerful means to assess the potential risks and benefits of gene therapy. The project involves a collaboration between Mercurna B.V., a biotech company specialized in developing mRNA therapeutics, and KU Leuven and Radboudumc that contribute expertise in rare genetic diseases and nanotechnology.

Chronic metabolic diseases present a major burden for both the individual and society. The majority of these diseases are inherited and are seldom with less than 1 in 2000 persons affected. Still 6-8% of the population suffers from one of the more than 6000 rare diseases that are currently known. For the majority of patients, gene therapy that involves the insertion of the correct genetic material will be the only possible cure. However, gene therapy is not always effective in every patient and may cause significant side-effects, which is an issue due to the irreversible nature of the treatment.

Protein expression through messenger RNA can achieve the same effect as gene therapy, but is temporary and thus reversible. Should the desired therapeutic effect not be achieved, or should side-effects occur, then the intervention can be stopped or adjusted without persisting risks for the patient. For the rare genetic disease cystinosis we will achieve the validation of our approach by a direct comparison of mRNA-mediated expression of the defective gene and viral delivery in cell and animal models of increasing complexity.

If successful, we expect that the results of this project will lead to a paradigm change in the development of viral gene therapy and thus to an acceleration in the development and application of gene therapy for rare chronic diseases and contribute to an affordable health care for patients with rare inherited disease and increase their participation within society