Abstract
Over the last decade, pioneering molecular gene therapy for inner-ear disorders have achieved experimental hearing improvements after a single local or systemic injection of adeno-associated, virus-derived vectors (rAAV for recombinant AAV) encoding an extra copy of a normal gene, or ribozymes used to modify a genome. These results hold promise for treating congenital or later-onset hearing loss resulting from monogenic disorders with gene therapy approaches in patients. In this review, we summarize the current state of rAAV-mediated inner-ear gene therapies including the choice of vectors and delivery routes, and discuss the prospects and obstacles for the future development of efficient clinical rAAV-mediated cochlear gene medicine therapy.
Highlights
Sensorineural hearing loss (SNHL) is one of the most prevalent sensory deficits in both childhood and adulthood, which affects approximately 466 million people worldwide and more than half of the population over 60 years of age
While intravenous injections of rAAV2/9 can transduce the cochlear and vestibular sensorineural cells [62] in mice, the possibility of recombinant adeno-associated virus (rAAV) vectors crossing the blood-labyrinth barrier to deliver DNA to cochlear target cells in larger mammals must be confirmed before its potential clinical translation
We summarize some successful results of rAAV-mediated expression of exogenous wild-type genes needed for inner ear function for treating congenital or early-onset hearing loss (Table 1)
Summary
Sensorineural hearing loss (SNHL) is one of the most prevalent sensory deficits in both childhood and adulthood, which affects approximately 466 million people worldwide and more than half of the population over 60 years of age This is estimated to rise to more than 900 million people by 2050 [1]. Some hearing rehabilitation is possible through hearing devices that can amplify sound, either by using conventional hearing aids in the case of mild or moderate deafness, or surgically-placed cochlear implants for severe bilateral deafness. The advantage of the latter is that it can bypass non-functional sensory hair cells by directly stimulating primary auditory neurons. We discuss the various strategies used in gene therapy, such as gene addition, silencing, and editing
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