Journal
GENE THERAPY
Volume 19, Issue 3, Pages 255-263Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2011.91
Keywords
adeno-associated viral vector; collagenase; round window membrane; cochlear gene transfection; hair cell; spiral ganglion neuron
Categories
Funding
- Natural Outstanding Youth Foundation of China [30925035]
- Ministry of Science and Technology, China [2009CB526504]
- National Natural Science Foundation of China [30901669]
Ask authors/readers for more resources
The auditory portion of the inner ear, the cochlea, is an ideal organ for local gene transfection owing to its relative isolation. Various carriers have been tested for cochlear gene transfection. To date, viral vectors appear to have much higher transfection efficacy than non-viral mechanisms. Among these vectors, recombinant adeno-associated virus (rAAV) vectors have several advantages such as being non-pathogenic and the ability to produce prolonged gene expression in various cell types. However, rAAV vectors cannot pass through the intact round window membrane (RWM), otherwise a very attractive approach to access the human inner ear. In this study, performed in guinea-pigs, we describe a method to increase the permeability of RWM to rAAV vectors by partial digestion with collagenase solution. Elevated delivery of rAAV across the partially digested RWM increased transfection efficacy to a satisfactory level, even though it was still lower than that achieved by direct cochleostomy injection. Functional tests (auditory brainstem responses) showed that this enzymatic manipulation did not cause permanent hearing loss if applied appropriately. Morphological observations suggested that the damage to RWM caused by partial digestion healed within four weeks. Taken together, these findings suggest that partial digestion of the RWM is a safe and effective method for increasing the transfection of cochlear sensory cells with rAAV. Gene Therapy (2012) 19, 255-263; doi:10.1038/gt.2011.91; published online 23 June 2011
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available