The promise of therapeutically targeting components of the matrix with powerful gene therapy approaches is elegantly examined in a report by Maruelli et al. using osteogenesis imperfecta (OI) as a congenital disease model in which dominant mutations in the genes encoding the α chains of collagen type I (COL1A1 and COL1A2) manifests as a rare brittle bone disease [55]. Here, COL1A1 is linked to osteogenesis imperfecta.