Project Structure & Methodology

The cmRNAbone project is structured in three main pillars aiming to:

  1. create new insights and solutions in the field of regenerative medicine (WP1–4),
  2. provide sound scientific assessment of the regenerative capacity of the proposed therapy (WP5–7), and
  3. develop regenerative application via preclinical proof of concepts and advance towards a regulatory and commercial path for a first in-human trial (WP8).

Thus, the following work packages have been defined:

WP1 - cmRNAs encoding proteins for bone regeneration in bone non-unions and osteoporotic patients

These results will provide the foundation for the envisaged gene therapy and will allow exploring the influence of combined cmRNAs on the regeneration processes in bone tissue repair

WP2 - Vectors for delivery of cmRNA that can be combined in biomaterials matrix for development of gene activated matrix regenerative approach

These results will deliver the basic needed regenerative elements to assess the gene therapy envisioned in this project.

WP3 - Advanced biomaterials guiding regenerative processes which will also function as 3D printed gene activated matrix

These results will provide a clear breakthrough as the first 3D printed GAM ever produced.

WP4 - 3D bioprinter solution with inbuilt design for ink and clinical setting

These results will strongly contribute to the consolidation of a novel 3D bioprinting formulation and its application to the clinic via dedicated printer system.

WP5-7 - In vitro and in vivo testing to assess and optimise the technologies’ potential in a large clustered work package

These results will lead to formulation candidates that will be assessed in relevant preclinical models.

WP8 - Proof of concepts for the cmRNAbone regenerative therapy

These results will demonstrate the potential of the new regenerative therapy.

cmRNAsin vitro transcription,purification, characterization,inducibility in Std assaysGMP-likeVector formulationsproduction & characterization,inducibility improvement in Stdassays, cytocomp., inducibilty inGAM. GMP-likeIn vitroassessements of single and combination of cmRNAs -Dose response.Mesenchymal stromal cells, osteoblasts, endothelial cells – hMSCs on topcmRNAs/vectors fHA-CaP -> induced protein released in media -> effect oncells (SNs, Ecs, hMSCs, pericytes, Osteo.);in vivoectopicassessement ofsinglecmRNAs High/Medium/Lowdose -subcut. Nude mice, 8 weeks, characterizedby histology, CTCombination of cmRNAs-vectors fHA-CaPin vivoproof of concepts.1. Critical bine size defect model. 8 weeks, CT, MRI, histology2. Bone defect in osteoporotic model, 8 weeks, CT, Biomeca., Gene Exp., histologySEMA3AVEGF/PDGF-bbBMP-7fHA-caPfHA and CaP synthesis andcharacterization,fHA/CaPformulationoptimization ofvisco-eleastic properties,cmRNA/vector loading/release,cells viability & ingrowth,GMP-likeExtrusion optimizationof WP3 formulation and3D printingparameters,design of device andfabrication ofprototypesWP 1WP 3WP 4WP 2WP 5–7WP 8