Figure 1.

Inner ear delivery of gene therapy. Shown are the major routes by which gene therapy can be delivered to the inner ear. With the RWM approach, a small needle is used to pierce the RWM and deliver vector directly into the perilymph. A ‘canalostomy’ is done by drilling a hole into a semicircular canal (usually the posterior canal) and inserting a canula into the hole. Vector is delivered into both endolymph and perilymph in one of two directions depending on the orientation of the cannula. A cochleostomy requires a hole in the bony labyrinth between round window and basal turn of cochlea. Vector is delivered into endolymph. The RWM + CF technique combines RWM injection with a CF, which functions as a vent to allow egress of fluid (red, endolymph; yellow, perilymph; blue arrow, expected flow of injected vectors through cochlea when RWM + CF is done; PSCC, posterior semicircular canal; ASCC, anterior semicircular canal; LSCC, lateral semicircular canal; OW, oval window; RW, round window).