Genetic Engineering Publications - GEG Tech top picks

A novel CRISPR-Cas9 approach that targets a damaging signaling pathway in the heart confers protection against ischemia and reperfusion injury, according to a study in mice. The findings suggest that gene editing could offer a permanent, advanced strategy for treating heart disease and even serve as an intervention to repair heart damage immediately after a heart attack. CRISPR-Cas9 gene editing has shown promise as a therapeutic approach for the treatment of rare inherited diseases. Chronic overactivation of Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) is known to cause several heart diseases in humans and mice, including lesions. The researchers found that using CRISPR-Cas9 adenine base editing to eliminate oxidative activation sites of the CaMKIIδ gene in cardiomyocytes protected them from IR injury in mouse models. In addition, the researchers found that injecting gene-editing reagents into mice shortly after IR injury allowed the animals to recover cardiac function after severe damage.

Current treatments of ventricular arrhythmias rely on modulation of cardiac electrical function through drugs, ablation or electroshocks, which are all non-biological and rather unspecific, irreversible or traumatizing interventions. Optogenetics, however, is a novel, biological technique allowing electrical modulation in a specific, reversible and trauma-free manner using light-gated ion channels. The aim of this study was to investigate optogenetic termination of ventricular arrhythmias in the whole heart.

The standard CAR T cell strategy would be problematic when directed against heart failure or other fibrotic diseases in humans.

Fibroblasts have a normal and important function in the body, particularly in wound healing. CAR T cells that are genetically reprogrammed to attack fibroblasts could survive in the body for months or even years, suppressing the fibroblast population and impairing wound healing for all that time. Therefore, in the new study published in Science, Epstein and colleagues designed a technique for a more temporary and controllable, and much more procedurally simple, type of CAR T cell therapy. They designed an mRNA that encodes a T-cell receptor targeting activated fibroblasts and encapsulated the mRNA in tiny bubble-like lipid nanoparticles, which are themselves coated with molecules that lodge in T cells. Injections of this therapy into mice modeling heart failure successfully reprogrammed a large population of mouse T cells, causing a major reduction in cardiac fibrosis in the animals and restoration of a mostly normal heart size and function with no sign of continued anti-fibroblast T cell activity one week after treatment. Researchers continue to test this mRNA-based transient CAR T-cell technology, with the hope of eventually starting clinical trials