CRISPR-GNDM

CRISPR-GNDM (Guide Nucleotide-Directed Modulation) is a proprietary epigenome editing technology developed by Modalis Therapeutics. Unlike traditional CRISPR-Cas9 systems that induce double-strand breaks to edit the genome, CRISPR-GNDM employs a catalytically inactive Cas protein (dCas) conjugated to an epigenetic repressor payload. This approach allows for the precise modulation of gene expression—specifically the silencing of pathogenic genes—without altering the underlying DNA sequence. The lead application of this technology, often referred to as MDL-101, targets the D4Z4 repeat array on chromosome 4 to suppress the expression of the DUX4 gene, which is the primary driver of Facioscapulohumeral Muscular Dystrophy (FSHD). The therapeutic is delivered to muscle tissues using engineered, muscle-selective adeno-associated virus (AAV) capsids.

Other names

GNDMGuide Nucleotide-Directed Modulation