MMBio · Molecular Tools for Nucleic Acid Manipulation for Biological Intervention

Molecular Tools for Nucleic Acid Manipulation for Biological Intervention

The action of genes is responsible for all organismal processes of life. If mutations in these genes arise, the processes may go wrong and lead to diseases. To treat such genetic malfunctions, it would be desirable to manipulate the deficient genes directly, but that requires novel reagents that can be administered without causing harm and are selective and efficient. Such novel reagents would have profound impact on disease prevention and cure and benefit society as they enable new approaches to disease treatment. The objective of MMBio is to provide the ability to ultimately cure cellular disease phenotypes by employing molecular, chemical and biological approaches to interfere gene expression precisely and selectively. MMBio will focus on unconventional new therapeutic approaches, namely “genetic” drugs that are typically based on oligonucleotides (ONs) or the action of genome-editing nuclease enzymes. Genetic drugs have the advantage that their design can be programmed to act at a specific target much more predictably than conceivable for small molecule drugs. The challenges of this ambitious scientific objective include the synthesis of drug conjugates (e.g. therapeutic antisense oligonucleotides), drug delivery reagents and artificial chemical and protein-based nucleases (e.g. the CRISPR/Cas system, a novel genetic pair of scissors with huge potential for genome editing), a quantitative mechanistic understanding of their action, efficient and selective delivery into the cell and consideration of the effects on disease development. To address this broad challenge MMBio brings together representatives of classically separate disciplines ranging from organic synthesis, mechanistic chemistry and nanochemistry to microengineering and experimental medicine. MMBio builds on a successful FP7 network that focused on fundamental aspects of phosphate transfer and recognition, and has now been extended to become a consortium covering the development pipeline of experimental drug conjugates from the reaction flask into cells. Many of the experimental approaches are rooted in Chemical Biology, a supradisciplinary field based on fundamental molecular research that employs selective intervention in biological systems by chemical means. But MMBio attempts to reach beyond this field, through consideration of the druggability of the constructs made and aiming, as far as possible, at the integration of in vitro, cell-based and in vivo studies. The network assembles experts in all the disciplines required across the entire R&D pipeline for the development of new gene therapeutics, including small and large private sector companies, academics focusing on fundamental and applied aspects and many opportunities for collaboration. The six industrial stakeholders in MMBio are ready to commercialize output of our network research.

Data: CORDIS, © European Union