Periodic Reporting for period 1 - Cor-Edit-P (Cardiac open reading frame edition to study cardiomyopathies in pigs)
Okres sprawozdawczy: 2022-01-01 do 2023-06-30
Exploiting unique and cutting-edge technology, Cor-edit-P aims at specifically eliminating the underlying cause of genetic DCM to improve cardiac function, reduce the risk of deadly arrhythmias and increase span and quality of life.
Cor-edit-P will
- generate currently lacking porcine models of genetic cardiomyopathy, using AAV-Cas9 to induce mutations in sarcomere genes, e.g. titin (TTN) and ß-myosin heavy chain (MYH7);
- exercise curative Crispr-Cas9 mediated gene editing of DCM in pigs in vivo, using the PLNR14del mutation in the phospholamban (PLN) gene as prominent example;
- use human patient-derived PLN-R14del ventricular progenitor cells for gene correction ex vivo followed by transplantation of corrected cells into PLN-R14del pigs.
Our approach implements a new paradigm for treating genetic cardiomyopathy and develops Crispr-Cas9 based gene therapy in pigs to foster clinical translation. Our work will influence the development of gene therapy by industry and academia and will benefit patients suffering genetic cardiomyopathy, but also further genetic diseases which are manifold prevalent in Europe.