Unconventional myosin-VIIa (MYO7A) (MYO7A)

Unconventional myosin-VIIa (MYO7A) is a member of the myosin superfamily of ATP-dependent motor proteins that move along actin filaments. It is primarily expressed in the pigment epithelium and photoreceptor cells of the retina, as well as the hair cells of the inner ear, where it is vital for intracellular trafficking and the maintenance of stereocilia (UniProt Q13402). Mutations in the MYO7A gene are the most common cause of Usher syndrome type 1B (USH1B), a genetic disorder characterized by congenital hearing loss and progressive vision loss due to retinitis pigmentosa (MedlinePlus). As a therapeutic target, MYO7A is the focus of gene replacement strategies aimed at restoring functional protein levels to prevent retinal degeneration. A significant hurdle in targeting MYO7A is its large cDNA size (approximately 6.7 kb), which exceeds the 4.7 kb capacity of standard adeno-associated virus (AAV) vectors. Consequently, clinical and preclinical efforts have utilized lentiviral vectors, such as SAR421869 (UshStat), or dual-AAV vector systems like ATSN-201 to deliver the full-length gene to the target retinal tissues (ClinicalTrials.gov NCT01505062; PMID: 30643202). These therapies aim to halt the progression of blindness by ensuring proper melanosome positioning and opsin transport within the photoreceptors.

Other names

Myosin-7AUSH1BDFNB2DFNA11NSRD2Myosin VIIA

Gene replacement therapy designed to deliver a functional copy of the MYO7A gene to retinal cells (RPE and photoreceptors) to restore Myosin-VIIa protein expression and intracellular transport functions.