Hyaluronic Acid Enhances Gene Delivery into the Cochlea
dc.contributor.author | Shibata, Seiji B. | en_US |
dc.contributor.author | Cortez, Sarah R. | en_US |
dc.contributor.author | Wiler, James A. | en_US |
dc.contributor.author | Swiderski, Donald L. | en_US |
dc.contributor.author | Raphael, Yehoash | en_US |
dc.date.accessioned | 2013-06-25T18:43:16Z | |
dc.date.available | 2013-06-25T18:43:16Z | |
dc.date.issued | 2012-03 | en_US |
dc.identifier.citation | Shibata, Seiji B.; Cortez, Sarah R.; Wiler, James A.; Swiderski, Donald L.; Raphael, Yehoash (2012). "Hyaluronic Acid Enhances Gene Delivery into the Cochlea." Human Gene Therapy 23(3): 302-310. <http://hdl.handle.net/2027.42/98453> | en_US |
dc.identifier.issn | 1043-0342 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/98453 | |
dc.description.abstract | Abstract Cochlear gene therapy can be a new avenue for the treatment of severe hearing loss by inducing regeneration or phenotypic rescue. One necessary step to establish this therapy is the development of a safe and feasible inoculation surgery, ideally without drilling the bony cochlear wall. The round window membrane (RWM) is accessible in the middle-ear space, but viral vectors placed on this membrane do not readily cross the membrane to the cochlear tissues. In an attempt to enhance permeability of the RWM, we applied hyaluronic acid (HA), a nontoxic and biodegradable reagent, onto the RWM of guinea pigs, prior to delivering an adenovirus carrying enhanced green fluorescent protein (eGFP) reporter gene (Ad-eGFP) at the same site. We examined distribution of eGFP in the cochlea 1 week after treatment, comparing delivery of the vector via the RWM, with or without HA, to delivery by a cochleostomy into the perilymph. We found that cochlear tissue treated with HA-assisted delivery of Ad-eGFP demonstrated wider expression of transgenes in cochlear cells than did tissue treated by cochleostomy injection. HA-assisted vector delivery facilitated expression in cells lining the scala media, which are less accessible and not transduced after perilymphatic injection. We assessed auditory function by measuring auditory brainstem responses and determined that thresholds were significantly better in the ears treated with HA-assisted Ad-eGFP placement on the RWM as compared with cochleostomy. Together, these data demonstrate that HA-assisted delivery of viral vectors provides an atraumatic and clinically feasible method to introduce transgenes into cochlear cells, thereby enhancing both research methods and future clinical application. | en_US |
dc.publisher | Mary Ann Liebert, Inc., publishers | en_US |
dc.title | Hyaluronic Acid Enhances Gene Delivery into the Cochlea | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Medicine (General) | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.identifier.pmid | 22074321 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/98453/1/hum%2E2011%2E086.pdf | |
dc.identifier.doi | 10.1089/hum.2011.086 | en_US |
dc.identifier.source | Human Gene Therapy | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.