Background and aim: Osteoarthritis (OA) is characterized by chronic joint pain and functional impairment and imposes a huge burden on the individual patient and health care systems. Current treatments relieve symptoms, but do not counteract disease progression. Intra-articular (in-joint) gene therapy-like mRNA therapy offers a promising highly innovative solution for the treatment of OA.
Despite their great promise, most of the current OA gene therapies rely on viral vectors for transfection, which are associated with high safety risks and costs, and have low transfection rates due to poor penetration in the extracellular matrices of joint tissues. This project proposes a novel approach, using polymer nanoparticle-based delivery of stabilized mRNA candidates. The patented nanotechnology of 20MED is combined with the proprietary stabilized non-immunogenic mRNA technology of ETHRIS, to deliver a non-viral mRNA-based ‘transcript therapy’ for injection into the joint. The preclinical efficacy will be tested in ex-vivo joint bioreactors and rat disease models by ARI and Paracelsus Medical University. The aim is to generate preclinical data with proof of concept for the novel mRNA transcript therapy.
Eurostars; ARI Funding EUR 200,000; Period 2019-2022.
PublicationZuncheddu D, Della Bella E, Petta D, Bärtschi C, Häckel S, Deml MC, Stoddart MJ, Grad S, Basoli V. Effect of glucose depletion and fructose administration during chondrogenic commitment in human bone marrow-derived stem cells. Stem Cell Res Ther. 2022;13(1):533. https://doi.org/10.1186/s13287-022-03214-2
PresentationBasoli V, Li Z, Traweger A, Sanchez J, Plank C, Rip J, Alini M, Grad S. Effect of nanoparticle-based mRNA delivery on modulation of inflammation in an osteochondral inflammation model. 2021 OARSI Connect virtual (poster)
Sturm L, Schwemberger B, Geiger J, Manish A, Dewi HS, Engbersen J, Rip J, Alini M, Traweger A, Grad S, Basoli V. Comparison of different transfection methods for mRNA delivery in articular joint cells. 2021 TERMIS world congress digital (poster)
Basoli V, Traweger A, Plank C, Rip J, Alini M, Grad S. Effect of therapeutic IL1Ra and IL10 mRNA vehiculated by polymeric nanoparticles in osteochondral ex-vivo model: a new approach for osteoarthritis treatment. ORS 2022 (poster). https://www.ors.org/Transactions/68/1497.pdf
Basoli V, Traweger A, Plank C, Rip J, Alini M, Grad S. Therapeutic mRNA for the treatment of osteoarthritis. Utopia or future strategy? 2023 ORS (poster)
Engbersen J, 20Med Therapeutics, NL
Planck C, Ethris Gmbh, DE
Traweger A, Paracelsus Medical University, AT