OTOF-GT

Introduction

What is OTOF-GT ?

Sensorion’s OTOF-GT gene therapy development program aims to restore hearing in people living with Otoferlin deficiency, one of the most common forms of congenital deafness. The Otoferlin gene is large and is delivered to the ear using two standard gene therapy vectors (AAV) and assembled in place.

This dual gene therapy approach has been proved in concept in preclinical studies: the two parts of the Otoferlin gene were successfully delivered in mice, the protein reassembled and hearing restored.

Source : https://www.pnas.org/content/116/10/4496

The Otoferlin protein is a major calcium sensor protein involved in synaptic exocytosis in sensory hair cells (inner hair cells)

OTOF is the gene coding for the Otoferlin protein, a Ca2+
sensor for vesicle fusion and vesicle pool replenishment
at auditory hair cell ribbon synapses

OTOF-GT

GENE THERAPY – DUAL AAV APPROACH

PRE-CLINICAL OTOF GENE THERAPY PROOF OF CONCEPT DURABLY RESTORES COCHLEAR RECEPTOR FUNCTION IN A KNOCK-OUT MOUSE MODEL

 

Immunostained inner hair cells in wild type, Otof -/- and Otof -/- injected with dual AAV2 quadY-F OTOF vector
Expression of otoferlin in cochlear receptors inner hair cells

Akil et al. 2019 (link)