Ablation of CaMKIId oxidation by CRISPR-Cas9 base editing as a therapy for cardiac disease

CRISPR-Cas9 gene editing is emerging as a prospective therapy for genomic mutations. However, current editing approaches are directed primarily toward relatively small cohorts of patients with specific mutations. Here, we describe a cardioprotective strategy potentially applicable to a broad range of patients with heart disease. We used base editing to ablate the oxidative activation sites of CaMKIId, a primary driver of cardiac disease. We show in cardiomyocytes derived from human induced pluripotent stem cells that editing the CaMKIId gene to eliminate oxidation-sensitive methionine residues confers protection from ischemia/reperfusion (IR) injury. Moreover, CaMKIId editing in mice at the time of IR enables the heart to recover function from otherwise severe damage. CaMKIId gene editing may thus represent a permanent and advanced strategy for heart disease therapy

Effect of crosslinking on the microtribological behavior of model polymer brushes

Polymer brushes in good solvents are known to exhibit excellent tribological properties. We have modeled polymer brushes and their gels using a multibead-spring model and studied their tribological behavior via nonequilibrium molecular-dynamics (MD) simulations. Simulations of brush- against-wall systems were performed using an implicit solvent-based approach. Polymer chains were modeled as linear chains, randomly grafted on a planar surface. Quantities extracted from the simulations are the normal stress, shear stress and concentration profiles. We find that while an increase in the degree of crosslinking leads to an increase in the coefficient of friction, an increase of the length of crosslinker chains does the opposite. Effect of crosslinking can be understood in two ways: (i) there are fewer polymer chains in the outer layer as the degree of crosslinking increases to take part in brush-assisted lubrication, and (ii) crosslinked polymer chains are more resistant to shear than non-crosslinked ones