Federal Grant Award Summary

The Trustees of Tufts College received a $374,866 Project Grant award from the National Center for Advancing Translational Sciences (NCATS, CFDA 93.350) effective August 1, 2026, through July 31, 2028. The project develops "Ribo-ATTECs" (ribonucleoprotein autophagy-targeting chimeras), a novel drug modality designed to achieve targeted lysosomal degradation of disease-causing RNA molecules. This research addresses a critical limitation in current RNA-targeting therapeutics by leveraging the natural cellular process of RNA autophagy (RNAPhagy) to degrade specific RNAs via the lysosomal pathway. The investigative team applies existing RNA-binding ligands—both small molecules and drug-like oligonucleotides—to create bifunctional compounds that recruit target RNAs to LC3/GABARAP autophagy proteins, enabling their transport to lysosomes for degradation by lysosomal ribonucleases.

The project establishes proof-of-concept for this RNA-degradation platform by targeting two disease-relevant RNA molecules: one implicated in Parkinson's disease progression and another serving as the causative agent in specific amyotrophic lateral sclerosis and frontotemporal dementia cases. Upon successful demonstration, the methodology will establish a generalizable platform capable of targeting any disease-associated RNA, substantially expanding the therapeutic scope beyond existing RNA-degradation approaches that are restricted to fewer than half of all disease-causing RNAs.