Sanford Burnham Prebys develops single-construct gene therapy to boost cardiac cell reprogramming in heart failure

[Sanford Burnham Prebys Medical Discovery Institute](https://app.allsci.com/organization/ASC-OH-0000000000108-1.0-1764853177), the La Jolla, California-based nonprofit research institute, has received a [USD 1.6 million NIH R01 grant](https://reporter.nih.gov/project-details/11298712) from the National Heart, Lung, and Blood Institute to develop a single-construct gene therapy aimed at improving cardiac reprogramming efficiency in heart failure. The award addresses a persistent bottleneck in cardiac regeneration research: existing reprogramming protocols convert only a small fraction of cardiac fibroblasts into functional cardiomyocyte-like cells, limiting their therapeutic utility. Principal investigator [Alexandre Romain Colas](https://app.allsci.com/researcher/ASC-PR-0000110502208-1.0-1778789922) will pursue a strategy that combines overexpression of three transcription factors — Mef2c, Gata4, and Tbx5 (MGT) — with simultaneous knockdown of ATF7IP, a gene identified through genome-wide screening as a barrier to reprogramming. Delivered via a single viral vector construct, the approach is designed to reduce scar tissue burden and improve contractile function following myocardial infarction. Preclinical validation is planned in both rodent and porcine models, supported by multi-omics profiling including ATAC-seq, ChIP-seq, and RNA sequencing. Cardiac fibrosis remains an area with no approved antifibrotic therapy specifically targeting post-infarction remodeling. Several academic groups and companies are pursuing direct cardiac reprogramming, including work building on earlier MGT factor combinations, but efficiency gains have been incremental. The single-construct design here aims to compress a two-component intervention into a delivery-ready format more amenable to eventual clinical translation. --- This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: [https://allsci.com/news/](https://allsci.com/news/) --- Spot something wrong? [Report an issue with this article](https://newsgen-prod.reframedata.com/feedback/gene-therapy-heart-failure-sanford-burnham-prebys)