Federal Project Grant Award Summary

The National Heart, Lung, and Blood Institute (NHLBI) awarded $570,666 to Icahn School of Medicine at Mount Sinai on July 1, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to develop an advanced base editor reengineering platform aimed at enhancing gene editing specificity and selectivity. The project will deliver a streamlined engineering platform that integrates naturally occurring oligonucleotide binding modules into deaminase active centers to minimize off-target activities and enable programmable editing selectivity. The research outputs will include a suite of improved base editors (IBEs) with refined activity windows and decreased off-target effects, advancing the potential therapeutic application of base editing for correcting genetic variants. The award will conclude on April 30, 2028.

Under two primary research aims, the awardee will generate engineered base editors with enhanced specificity, develop alternative deaminases with improved targeting capabilities, and validate editing efficiency and outcomes in cystic fibrosis disease models. Specifically, Aim 1 focuses on advancing the base editor reengineering platform to minimize off-target activities and optimize editing selectivity, while Aim 2 will assess the efficacy of the improved base editors in correcting diverse cystic fibrosis transmembrane conductance regulator (CFTR) nonsense mutations in cell and animal models. Upon successful completion, the project will provide a roadmap for designing and engineering therapeutic base editors applicable to a broad spectrum of genetic diseases.