Helper-Dependent Adenovirus-Mediated Gene Transfer Into the Adult Mouse Cochlea

Wenzel, Gentiana I.; Xia, Anping; Funk, Etai; Evans, M. Bradley; Palmer, D. Jason; Ng, Philip; Pereira, Fred A.; Oghalai, John S.

doi:10.1097/mao.0b013e318158973f

Cited by 32 publications

(24 citation statements)

References 41 publications

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“…The ABR signal was measured with a bioamplifier (DB4, TuckerDavis Technologies) from a needle electrode positioned at the ventral surface of the tympanic bulla referenced to an electrode placed at the vertex of the skull, as described previously (Wenzel et al, 2007a;Wenzel et al, 2007b). A ground electrode was placed in the hind leg.…”

Section: Auditory Brainstem Response (Abr) Measurementsmentioning

confidence: 99%

Deficient forward transduction and enhanced reverse transduction in the alpha tectorin C1509G human hearing loss mutation

Xia

Gao

Tao

et al. 2010

Disease Models &Amp; Mechanisms

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SUMMARYMost forms of hearing loss are associated with loss of cochlear outer hair cells (OHCs). OHCs require the tectorial membrane (TM) for stereociliary bundle stimulation (forward transduction) and active feedback (reverse transduction). Alpha tectorin is a protein constituent of the TM and the C1509G mutation in alpha tectorin in humans results in autosomal dominant hearing loss. We engineered and validated this mutation in mice and found that the TM was shortened in heterozygous Tecta C1509G/+ mice, reaching only the first row of OHCs. Thus, deficient forward transduction renders OHCs within the second and third rows non-functional, producing partial hearing loss. Surprisingly, both Tecta C1509G/+ and Tecta C1509G/C1509G mice were found to have increased reverse transduction as assessed by sound-and electrically-evoked otoacoustic emissions. We show that an increase in prestin, a protein necessary for electromotility, in all three rows of OHCs underlies this phenomenon. This mouse model demonstrates a human hearing loss mutation in which OHC function is altered through a non-cell-autonomous variation in prestin.

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Section: Auditory Brainstem Response (Abr) Measurementsmentioning

confidence: 99%

Deficient forward transduction and enhanced reverse transduction in the alpha tectorin C1509G human hearing loss mutation

Xia

Gao

Tao

et al. 2010

Disease Models &Amp; Mechanisms

Self Cite

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“…Access to the perilymph by diffusion across the round window membrane, thereby preserving cochlear integrity, is possible for Ad and non-viral liposomes but not AAV [41] , but is not as efficient as direct injection of the vector into the scala tympani [97] . Although surgically more difficult, injection of gene transfer vehicles directly into the scala media results in efficient transduction of hair cells and supporting cells but risks damage and loss of hair cells around the injection site [87,98,99] . Viral vector access to the cochlea can be achieved via the vestibular organs, helping to reduce trauma to the cochlea and subsequent hearing loss.…”

Section: Delivery Sites For Gene Transfer Vectorsmentioning

confidence: 99%

Novel drug delivery systems for inner ear protection and regeneration after hearing loss

Richardson

Wise

Andrew

et al. 2008

Expert Opinion on Drug Delivery

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Background : A cochlear implant, the only current treatment for restoring auditory perception after severe or profound sensorineural hearing loss (SNHL), works by electrically stimulating spiral ganglion neurons (SGNs). However, gradual degeneration of SGNs associated with SNHL can compromise the efficacy of the device. Objective : To review novel drug delivery systems for preserving and/or regenerating sensory cells in the cochlea after SNHL. Methods : The effectiveness of traditional cochlear drug delivery systems is compared to newer techniques such as cell, polymer and gene transfer technologies. Special requirements for local drug delivery to the cochlea are discussed, such as protecting residual hearing and site-specific drug delivery for cell preservation and regeneration. Results/conclusions : Drug delivery systems with the potential for immediate clinical translation, as well as those that will contribute to the future of hearing preservation or cochlear cellular regeneration, are identified.

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“…It has the advantages of allowing the maximal amount of drug/gene to enter the inner ear with minimal systemic interference. Numerous reports have been published on the successful delivery via this approach of various foreign genes and genetically engineered therapeutic cells into inner ears, mediated by various vectors (Stover et al, 2000;Oshima et al, 2004;Okano et al, 2006;Akin et al, 2007;Kanzaki et al, 2007;Liu et al, 2007;Wenzel et al, 2007). Inner ear perfusion with a osmotic micropump may be a reasonable choice for continuing and steady delivery of a foreign gene (Luebke et al, 2001).…”

Section: Routes Of Administration For Inner Ear Gene Therapymentioning

confidence: 99%

Current Status and Prospects of Gene Therapy for the Inner Ear

2011

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Inner ear diseases are common and often result in hearing disability. Sensorineural hearing loss is the main cause of hearing disability. So far, no effective treatment is available although some patients may benefit from a hearing aid equipped with a hearing amplifier or from cochlear implantation. Inner ear gene therapy has become an emerging field of study for the treatment of hearing disability. Numerous new discoveries and tremendous advances have been made in inner ear gene therapy including gene vectors, routes of administration, and therapeutic genes and targets. Gene therapy may become a treatment option for inner ear diseases in the near future. In this review, we summarize the current state of inner ear gene therapy including gene vectors, delivery routes, and therapeutic genes and targets by examining and analyzing publications on inner ear gene therapy from the literature and patent documents, and identify promising patents, novel techniques, and vital research projects. We also discuss the progress and prospects of inner ear gene therapy, the advances and shortcomings, with possible solutions in this field of research.

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Helper-Dependent Adenovirus-Mediated Gene Transfer Into the Adult Mouse Cochlea

Abstract: The technique of scala media HDAd injection reliably infects the adult mouse cochlea, including cells within the organ of Corti, although the procedure itself adversely affects hearing.

Cited by 32 publications

References 41 publications

Deficient forward transduction and enhanced reverse transduction in the alpha tectorin C1509G human hearing loss mutation

Deficient forward transduction and enhanced reverse transduction in the alpha tectorin C1509G human hearing loss mutation

Novel drug delivery systems for inner ear protection and regeneration after hearing loss

Current Status and Prospects of Gene Therapy for the Inner Ear

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