Types of HHL
This term describes hearing loss that occurs alongside symptoms in other organ systems, such as the eyes or heart.
Syndromic HL (SHL)
This cochlear cell type is responsible for mechanoelectrical transduction via stereocilia and is the target of more than half of all deafness genes.
Hair cells (HCs)
This strategy delivers a functional copy of a defective gene and is best suited for loss-of-function, recessive mutations.
Gene replacement
This delivery route is the most common in inner ear gene therapy and requires no drilling — it accesses the perilymph by piercing an existing membrane.
Round window membrane (RWM)
This inheritance pattern accounts for 75–80% of non-syndromic hereditary hearing loss cases.
Autosomal recessive
These cells surround hair cells, maintain their structural integrity, and recycle potassium and neurotransmitters — mutations in GJB2 affect them.
Supporting cells (SCs)
This gene therapy strategy silences or reduces mutant gene expression at the RNA level without altering the DNA sequence, using tools like ASOs or RNAi.
Gene suppression
This route offers the highest transduction efficiency of any delivery method and is the only one that reliably reaches stria vascularis marginal cells, but carries the highest trauma risk due to drilling.
Cochleostomy
This syndrome combines sensorineural hearing loss, retinitis pigmentosa, and vestibular dysfunction, and is the most common cause of combined deafness and blindness.
Usher syndrome (USH)
This cochlear structure maintains a high K+ concentration in the endolymph by pumping ions across three cell layers, and mutations in KCNQ1 and KCNE1 disrupt its function.
Stria vascularis (SV)
This gene therapy strategy directly alters the DNA sequence at the mutation site and is the only approach that can offer permanent correction.
Gene editing
This route drills into the posterior semicircular canal to access both the cochlea and vestibule, and is a common alternative to RWM in adult mice.
Canalostomy