We propose a new therapeutic approach with disease-modifying potential: treating patients with asthma with autologous monocyte-derived Macrophages (Macs) in which PLA2G5 has been removed using CRISPR technology.

PLA2G5 is a master regulator of macrophage activation,  producing a broad spectrum of proinflammatory mediators, including bioactive lipids, cytokines, and chemokines. After depletion of PLA2G5 by CRISPR, Macs will be reintroduced into the patient by intrabronchial administration, granting exclusive homing into the lungs. These modified Macs will halt inflammation (asthma exacerbations), improve lung functions (FEV1), and prevent chronicization, providing a potent and lasting treatment for asthma.

This technology will drastically change the treatment of asthma by reducing the amount and types of medications, the number of visits to doctors and the ER, and health care costs in general. While most therapies inhibit one proinflammatory mediator, this treatment would offer an alternative approach by targeting multiple mediators and enhancing endogenous anti-inflammatory mechanisms. Because transplanted macrophages can survive in the lung for up to 9 months without migrating to other organs, this approach should offer a highly efficacious and durable treatment for asthma.