Federal Project Grant Award Summary

The University of Pennsylvania received a $406,250 Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), awarded March 2, 2026, with a completion date of December 31, 2030. The grant funds a five-year research program to advance nucleic acid chemistry and develop novel xeno nucleic acids (XNAs)—synthetic nucleic acid analogs with modified backbones—to expand the genetic toolkit for RNA silencing and editing applications. The research builds upon the investigator's prior work in chemical modifications of nucleobases and sugar backbones to create functional XNA molecules that demonstrate enhanced thermal stability, nuclease resistance, and biocompatibility.

The primary deliverables include the development of an innovative XNA-SELEX (in vitro selection) platform to generate functional XNA molecules and the design of novel XNAzymes and XNA aptamers based on 3-NP-DNA (N3-P5 linked phosphoramidate DNA) and 2-F-RNA (2-fluoro-RNA). These research products are intended to address current limitations in allele-specific RNA silencing and site-directed adenosine-to-inosine (A-to-I) RNA editing, laying a foundation for next-generation RNA therapeutics applicable to genetic disorders caused by single-point mutations. The research is conducted at the University of Pennsylvania's Philadelphia campus and contributes to NIGMS's core mission of supporting fundamental biomedical research that advances understanding of biological processes and disease treatment development.