Gene therapy of the inner ear M Pfister, A K Lalwani

2007 ◽  
pp. 309-314
Keyword(s):  
Gene Therapy ◽  
Inner Ear

scholarly journals Gene therapy via canalostomy approach preserves auditory and vestibular functions in a mouse model of Jervell and Lange-Nielsen syndrome type 2

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xuewen Wu ◽  
Li Zhang ◽  
Yihui Li ◽  
Wenjuan Zhang ◽  
Jianjun Wang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mouse Model ◽  
Inner Ear ◽  
Viral Vectors ◽  
Survival Rates ◽  
Semicircular Canals ◽  
Dependent Manner ◽  
Syndrome Type ◽  
Dose Dependent

AbstractMutations in voltage-gated potassium channel KCNE1 cause Jervell and Lange-Nielsen syndrome type 2 (JLNS2), resulting in congenital deafness and vestibular dysfunction. We conducted gene therapy by injecting viral vectors using the canalostomy approach in Kcne1−/− mice to treat both the hearing and vestibular symptoms. Results showed early treatment prevented collapse of the Reissner’s membrane and vestibular wall, retained the normal size of the semicircular canals, and prevented the degeneration of inner ear cells. In a dose-dependent manner, the treatment preserved auditory (16 out of 20 mice) and vestibular (20/20) functions in mice treated with the high-dosage for at least five months. In the low-dosage group, a subgroup of mice (13/20) showed improvements only in the vestibular functions. Results supported that highly efficient transduction is one of the key factors for achieving the efficacy and maintaining the long-term therapeutic effect. Secondary outcomes of treatment included improved birth and litter survival rates. Our results demonstrated that gene therapy via the canalostomy approach, which has been considered to be one of the more feasible delivery methods for human inner ear gene therapy, preserved auditory and vestibular functions in a dose-dependent manner in a mouse model of JLNS2.

scholarly journals Advances and challenges in adeno-associated viral inner-ear gene therapy for sensorineural hearing loss

2021 ◽  
Vol 21 ◽  
pp. 209-236
Author(s):  
Kamakshi Bankoti ◽  
Charles Generotti ◽  
Tiffany Hwa ◽  
Lili Wang ◽  
Bert W. O’Malley ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Inner Ear ◽  
Sensorineural Hearing

scholarly journals AAV2.7m8 is a powerful viral vector for inner ear gene therapy

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Kevin Isgrig ◽  
Devin S. McDougald ◽  
Jianliang Zhu ◽  
Hong Jun Wang ◽  
Jean Bennett ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Inner Ear ◽  
Viral Vector

scholarly journals Gene therapy for hearing loss

2019 ◽  
Vol 28 (R1) ◽  
pp. R65-R79 ◽  
Author(s):  
Ryotaro Omichi ◽  
Seiji B Shibata ◽  
Cynthia C Morton ◽  
Richard J H Smith
Keyword(s):  
Gene Therapy ◽  
Hearing Loss ◽  
Inner Ear ◽  
Viral Vectors ◽  
Therapeutic Potential ◽  
Late Onset ◽  
Science Research ◽  
Gene Replacement ◽  
Age Related ◽  
Genetic And Environmental Factors

Abstract Sensorineural hearing loss (SNHL) is the most common sensory disorder. Its underlying etiologies include a broad spectrum of genetic and environmental factors that can lead to hearing loss that is congenital or late onset, stable or progressive, drug related, noise induced, age related, traumatic or post-infectious. Habilitation options typically focus on amplification using wearable or implantable devices; however exciting new gene-therapy-based strategies to restore and prevent SNHL are actively under investigation. Recent proof-of-principle studies demonstrate the potential therapeutic potential of molecular agents delivered to the inner ear to ameliorate different types of SNHL. Correcting or preventing underlying genetic forms of hearing loss is poised to become a reality. Herein, we review molecular therapies for hearing loss such as gene replacement, antisense oligonucleotides, RNA interference and CRISPR-based gene editing. We discuss delivery methods, techniques and viral vectors employed for inner ear gene therapy and the advancements in this field that are paving the way for basic science research discoveries to transition to clinical trials.

Drug delivery to the inner ear using gene therapy

2004 ◽  
Vol 37 (5) ◽  
pp. 1091-1108 ◽  
Author(s):  
Hinrich Staecker ◽  
Douglas E. Brough ◽  
Mark Praetorius ◽  
Kim Baker
Keyword(s):  
Drug Delivery ◽  
Gene Therapy ◽  
Inner Ear

scholarly journals Effects of Microbubble Size on Ultrasound-Mediated Gene Transfection in Auditory Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Ai-Ho Liao ◽  
Yi-Lei Hsieh ◽  
Hsin-Chiao Ho ◽  
Hang-Kang Chen ◽  
Yi-Chun Lin ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Hearing Loss ◽  
Gene Transfer ◽  
Inner Ear ◽  
Hair Cells ◽  
Gene Transfection ◽  
Effective Technique ◽  
Size Dependent ◽  
Genes Encoding

Gene therapy for sensorineural hearing loss has recently been used to insert genes encoding functional proteins to preserve, protect, or even regenerate hair cells in the inner ear. Our previous study demonstrated a microbubble- (MB-)facilitated ultrasound (US) technique for delivering therapeutic medication to the inner ear. The present study investigated whether MB-US techniques help to enhance the efficiency of gene transfection by means of cationic liposomes on HEI-OC1 auditory cells and whether MBs of different sizes affect such efficiency. Our results demonstrated that the size of MBs was proportional to the concentration of albumin or dextrose. At a constant US power density, using 0.66, 1.32, and 2.83 μm albumin-shelled MBs increased the transfection rate as compared to the control by 30.6%, 54.1%, and 84.7%, respectively; likewise, using 1.39, 2.12, and 3.47 μm albumin-dextrose-shelled MBs increased the transfection rates by 15.9%, 34.3%, and 82.7%, respectively. The results indicate that MB-US is an effective technique to facilitate gene transfer on auditory cellsin vitro. Such size-dependent MB oscillation behavior in the presence of US plays a role in enhancing gene transfer, and by manipulating the concentration of albumin or dextrose, MBs of different sizes can be produced.

scholarly journals An in vitro model system to study gene therapy in the human inner ear

Gene Therapy ◽  
2007 ◽  
Vol 14 (15) ◽  
pp. 1121-1131 ◽  
Author(s):  
B W Kesser ◽  
G T Hashisaki ◽  
K Fletcher ◽  
H Eppard ◽  
J R Holt
Keyword(s):  
Gene Therapy ◽  
Inner Ear ◽  
In Vitro Model ◽  
Model System ◽  
In Vitro Model System ◽  
Vitro Model ◽  
Human Inner Ear

scholarly journals Local gene therapy durably restores vestibular function in a mouse model of Usher syndrome type 1G

2017 ◽  
Vol 114 (36) ◽  
pp. 9695-9700 ◽  
Author(s):  
Alice Emptoz ◽  
Vincent Michel ◽  
Andrea Lelli ◽  
Omar Akil ◽  
Jacques Boutet de Monvel ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mouse Model ◽  
Inner Ear ◽  
Usher Syndrome ◽  
Vestibular Function ◽  
Gene Replacement ◽  
Syndrome Type ◽  
Mechanoelectrical Transduction ◽  
Efficient Gene ◽  
Usher Syndrome Type

Our understanding of the mechanisms underlying inherited forms of inner ear deficits has considerably improved during the past 20 y, but we are still far from curative treatments. We investigated gene replacement as a strategy for restoring inner ear functions in a mouse model of Usher syndrome type 1G, characterized by congenital profound deafness and balance disorders. These mice lack the scaffold protein sans, which is involved both in the morphogenesis of the stereociliary bundle, the sensory antenna of inner ear hair cells, and in the mechanoelectrical transduction process. We show that a single delivery of the sans cDNA by the adenoassociated virus 8 to the inner ear of newborn mutant mice reestablishes the expression and targeting of the protein to the tips of stereocilia. The therapeutic gene restores the architecture and mechanosensitivity of stereociliary bundles, improves hearing thresholds, and durably rescues these mice from the balance defects. Our results open up new perspectives for efficient gene therapy of cochlear and vestibular disorders by showing that even severe dysmorphogenesis of stereociliary bundles can be corrected.

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