LETI-101

LETI-101 is an experimental, allele-selective gene-editing therapy developed for the treatment of Huntington’s disease. It utilizes Life Edit’s proprietary CRISPR nuclease technology delivered via an adeno-associated virus serotype 5 (AAV5) vector to selectively target and edit the mutant huntingtin (HTT) gene at a specific exonic single nucleotide polymorphism (SNP), rs362331, which allows discrimination between the mutant and wild-type alleles. This approach enables selective reduction of disease-causing mutant HTT protein while preserving essential wild-type HTT protein, which is critical for normal cellular function. Preclinical studies in cell models, transgenic mice, and nonhuman primates have demonstrated robust dose-dependent reductions in mutant HTT protein levels—exceeding 80% in some brain regions—without significant off-target effects or safety concerns. The therapy is designed as a one-time treatment with potential long-lasting benefit by making permanent modifications to DNA[1][2][3][4][5][6][7].