Novel Approach To Treating Rare Disease Using An AAV Vector To Deliver Gene Editing Tools To The Brain

LETI-101, an AAV5-delivered gene editing therapy developed by Life Edit Therapeutics, targets the mutant huntingtin (HTT) gene to address Huntington’s Disease, a rare neurodegenerative disorder with no current disease-modifying treatments.

LETI-101 uses a Life Edit® nuclease guide RNA for allele-specific editing, aiming for a ≥ 40% reduction in mutant HTT protein while preserving wild-type HTT. Preclinical studies have shown significant reductions in mutant HTT protein in BACHD transgenic mice, and vector construct optimization has led to improved on-target editing and AAV transfection efficiency. The therapy also demonstrated favorable tolerability in cynomolgus monkeys, with no adverse clinical observations.

Efforts focused on manufacturability have resulted in the development of high-productivity AAV5 vectors, achieving a two-fold improvement in vector yield and full capsid production. The successful scale-up to 50 L for both upstream and downstream processes underscores LETI-101's potential for clinical translation. To learn more, access the full presentation below.