Cochlear gene delivery through an intact round window membrane in mouse.
Cochlear gene transfer studies in animal models have utilized mainly two delivery methods: direct injection through the round window membrane (RWM) or intracochlear infusion through a cochleostomy. However, the surgical trauma, inflammation, and hearing loss associated with these methods lead us to investigate a less invasive delivery method. Herein, we studied the feasibility of a vector transgene-soaked gelatin sponge, Gelfoam, for transgene delivery into the mouse cochlea through an intact RWM. The Gelfoam absorbed with liposomes and adenovirus, but not with adeno-associated virus (AAV), was successful in mediating transgene expression across an intact RWM in a variety of cochlear tissues. The Gelfoam technique proved to be an easy, atraumatic, and effective, but vector-dependent, method of delivering transgenes through an intact RWM. Compared with the more invasive gene delivery methods, this technique represents a safer and a more clinically viable route of cochlear gene delivery in humans.
Jero
J
J
Laboratory of Molecular Otology, Epstein Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA 94143, USA.
Mhatre
A N
AN
Tseng
C J
CJ
Stern
R E
RE
Coling
D E
DE
Goldstein
J A
JA
Hong
K
K
Zheng
W W
WW
Hoque
A T
AT
Lalwani
A K
AK
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003051:Cochlea / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D004423:Ear / Q000502:physiology; D004594:Electrophysiology; D005240:Feasibility Studies; D005781:Gelatin Sponge, Absorbable / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008081:Liposomes / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D012405:Round Window, Ear / Q000378:metabolism*; D014162:Transfection; D019076:Transgenes
D018076:DNA, Complementary; D008081:Liposomes; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins