Project description DEENESFRITPL Engineering a lung mycobacterium as a vector for the treatment of idiopathic pulmonary fibrosis Dysregulation of immunomodulatory molecules plays an essential role in many pulmonary diseases, including infections, lung cancer and idiopathic pulmonary fibrosis (IPF). In the case of IPF, inflammation results in senescence of the alveolar cells with telomere shortening and dysregulation of miRNAs. Modulating the immune response could provide a treatment for lung diseases. The EU-funded LUNG BIOREPAIR project aims to engineer the Mycovector, the genome-reduced lung bacterium Mycoplasma pneumoniae, as a vector to deliver protein-RNA complexes and express immunomodulatory proteins in alveolar cells. The project will use the non-pathogenic engineered version of Mycovector expressing different combinations of active biomolecules to treat bleomycin induced IPF in mice. Show the project objective Hide the project objective Objective Lung diseases are a leading cause of mortality worldwide. Dysregulation of immunomodulatory molecules plays a key role in many pulmonary diseases, including lung cancer, idiopathic pulmonary fibrosis (IPF) and infections. In IPF acute or chronic inflammation results in senescence of the alveolar cells with telomere shortening and/or dysregulation of miRNAs. Modulating the immune response directly or its downstream repercussions could be a possible way to help treat lung diseases. Systemic treatment with immunomodulatory molecules however, can have several drawbacks and include toxic side effects in other organs, the need for continuous delivery and a high cost of production. Similarly, treating immunomodulatory repercussions such as telomere shortening or abnormal miRNA expression in target cells is not easy due to the lack of a technology that efficiently and specifically delivers RNA. Furthermore, viral transformation can result in toxicity and is associated with high costs. To circumvent these problems, we aim to engineer the genome-reduced lung bacterium Mycoplasma pneumoniae as a vector to locally express immunomodulatory proteins, and/or to deliver protein¬–RNA complexes into alveolar cells (Mycovector). M. pneumoniae does not have a cell wall, it directly releases secreted biomolecules into the medium, it does not recombine, it has a unique genetic code that prevents the transfer of genes to other bacteria and we have a non-pathogenic engineered version of it. To design this Mycovector, we will combine our experience in this organism with our know-how in protein design (http://foldxsuite.crg.eu/). We will use our Mycovector expressing different combinations of active biomolecules to treat bleomycin-induced IPF in mice. This project will not only offer new insights into the treatment of a currently incurable disease, but also show that bacterial chassis can be used in other organs different from the gut paving the way to other applications in human health. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesclinical medicineoncologylung cancernatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticsRNA Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2020-ADG - ERC ADVANCED GRANT Call for proposal ERC-2020-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Coordinator FUNDACIO CENTRE DE REGULACIO GENOMICA Net EU contribution € 2 973 296,00 Address Carrer doctor aiguader 88 08003 Barcelona Spain See on map Region Este Cataluña Barcelona Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all FUNDACIO CENTRE DE REGULACIO GENOMICA Spain Net EU contribution € 2 973 296,00 Address Carrer doctor aiguader 88 08003 Barcelona See on map Region Este Cataluña Barcelona Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
