Abstract：
:Owing to the advances in transgenic animal technology and the advent of the next-generation sequencing era, over 120 genes causing hereditary hearing loss have been identified by now. In parallel, the field of human gene therapy continues to make exciting and rapid progress, culminating in the recent approval of several ex vivo and in vivo applications. Despite these encouraging developments and the growing interest in causative treatments for hearing disorders, gene therapeutic interventions in the inner ear remain in their infancy and await clinical translation. This review focuses on the adeno-associated virus (AAV), which nowadays represents one of the safest and most promising vectors in gene therapy. We first provide an overview of AAV biology and outline the principles of therapeutic gene transfer with recombinant AAV vectors, before pointing out major challenges and solutions for clinical translation including vector manufacturing and species translatability. Finally, we highlight seminal technologies for engineering and selection of next-generation "designer" AAV capsids, and illustrate their power and potential with recent examples of their application for inner ear gene transfer in animals.
journal_name
Hear Resjournal_title
Hearing researchauthors
Fakhiri J,Landegger LD,Grimm Ddoi
10.1016/j.heares.2020.108092subject
Has Abstractpub_date
2020-10-15 00:00:00pages
108092eissn
0378-5955issn
1878-5891pii
S0378-5955(20)30363-4pub_type
杂志文章,评审相关文献
HEARING RESEARCH文献大全abstract：:Acetylcholine (ACh) is a neuromodulator that is likely to play a role in plasticity as well as other phenomena at many sites in the auditory system. The auditory cortex receives cholinergic innervation from the basal forebrain, whereas the cochlea receives cholinergic innervation from the superior olivary complex. Muc...
journal_title：Hearing research
pub_type： 杂志文章,评审
doi：10.1016/j.heares.2010.12.019
更新日期：2011-09-01 00:00:00
abstract：:High doses of salicylate induce reversible tinnitus in experimental animals and humans, and is a common tinnitus model. Salicylate probably acts centrally and induces hyperactivity in specific auditory brainstem areas like the dorsal cochlear nucleus (DCN). However, little is known about the effect of high doses of sa...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/j.heares.2015.10.008
更新日期：2016-02-01 00:00:00
abstract：:Sodium salicylate (SS) can penetrate the blood-brain barrier to target neurons in the central auditory system. Understanding how SS alters functional behaviors of different types of central auditory neurons will provide insights into the neural mechanisms of SS-induced tinnitus. Here, we report the differential effect...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/j.heares.2009.03.007
更新日期：2009-07-01 00:00:00
abstract：:Exposure to harsh environment induces stress reactions that increase probability of survival. Stress influences the endocrine, nervous and immune systems and affects the functioning of a variety of organs. Numerous researchers demonstrated that a 24-h exposure to an acoustic rodent repellent provokes stress reaction i...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/j.heares.2009.10.006
更新日期：2010-01-01 00:00:00
abstract：:This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. ...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/j.heares.2009.09.016
更新日期：2009-10-07 00:00:00
abstract：:In recent years, new designs of cochlear implant electrodes have been introduced in an attempt to improve efficiency and performance by locating stimulation sites closer to spiral ganglion neurons and deeper into the scala tympani. The goal of this study was to document insertion depth, intracochlear position and inse...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/j.heares.2004.11.006
更新日期：2005-05-01 00:00:00
abstract：:One role of the inferior colliculus (IC) in bats is to create neuronal delay-tuning, which is used for the estimation of target distance in the echolocating bat's auditory system. In this study, we describe response properties of IC delay-tuned neurons of the mustached bat (Pteronotus parnellii) and compare it with th...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/j.heares.2012.02.013
更新日期：2012-04-01 00:00:00
abstract：OBJECTIVE:To objectively measure speech intelligibility of individual subjects from the EEG, based on cortical tracking of different representations of speech: low-level acoustical, higher-level discrete, or a combination. To compare each model's prediction of the speech reception threshold (SRT) for each individual wi...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/j.heares.2019.05.006
更新日期：2019-09-01 00:00:00
abstract：:Using transgenic fluorescent reporter mice in combination with an established tissue clearing method, we detail heretofore optically opaque regions of the spiral lamina and spiral limbus where the auditory peripheral nervous system is located and provide insight into changes in cochlear vascular density with ageing. W...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/j.heares.2018.11.012
更新日期：2019-01-01 00:00:00
abstract：:Binaural temporal resolution was measured using the discrimination of brief interaural time delays (ITDs). In experiment 1, three listeners performed a 2I-2AFC, ITD-discrimination procedure. ITD changes of 8 to 1024micros were applied to brief probe noises. These probes, with durations of 16 to 362ms, were placed symm...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/j.heares.2008.12.001
更新日期：2009-02-01 00:00:00
abstract：:Recordings were made from 185 neurons in the primary auditory cortex of cats in the age range of 15 to 297 days. A comparison was made between the tuning for click repetition-rate and for amplitude modulation-frequency of a noise burst on the basis of temporal Modulation Transfer Functions (tMTF). 90 of the 185 units ...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/0378-5955(93)90212-j
更新日期：1993-02-01 00:00:00
abstract：:The cerebellum is historically considered to be involved in motor control and motor learning. However, it is also a site of multimodal sensory and sensory-motor integration, implicated in auditory processing. The flocculus and paraflocculus are small lobes of the cerebellum, in humans located in the cerebellopontine a...
journal_title：Hearing research
pub_type： 杂志文章,评审
doi：10.1016/j.heares.2020.108081
更新日期：2020-12-01 00:00:00
abstract：:Immunolabeling of heregulin, a growth factor that enhances cell proliferation in damaged utricles, and one of its binding receptors, ErbB-2, has been briefly described in the P3 rat cochlea and utricle [Zheng et al. (1999) J. Neurocytol. 28, 901-912]. However, little is known about the distribution of heregulin and it...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/s0378-5955(02)00339-8
更新日期：2002-07-01 00:00:00
abstract：:Cochlear outer hair cell (OHC) electromotility is associated with the cell's lateral wall. The lateral wall contains two distinct membranes: the plasma membrane (PM) and the subsurface cisternae (SSC). We explored biophysical characteristics of these lipid structures using membrane-specific fluorescent dyes. We have p...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/s0378-5955(99)00077-5
更新日期：1999-09-01 00:00:00
abstract：:It is known that adrenocorticotrophic hormone (ACTH)-derived peptides, the so-called melanocortins, can reduce cisplatin-induced neurotoxicity. Recently, our group has found that cisplatin-induced ototoxicity can also be reduced or prevented by treatment with the synthetic melanocortin-like peptide, ORG 2766 (Hamers e...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/s0378-5955(98)00194-4
更新日期：1999-02-01 00:00:00
abstract：:Cyclic histograms of the responses of single auditory ganglion cells in the guinea pig were recorded during stimulation with amplitude modulated tones. Modulation frequencies ranged from 10 Hz to 800 Hz. The response histograms, phase-locked to the modulation signals, were analysed for mean action potential rate and f...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/0378-5955(87)90003-7
更新日期：1987-01-01 00:00:00
abstract：:Little is known about inner ear development in pigeons. This paper addresses the question of maturation in activity patterns of pigeon auditory nerve fibres, Pigeons that were 1, 2 and 4 weeks and 1, 2, 3 and 4 years old were investigated. Adult-like activity patterns are found 4 weeks post-hatching. Spontaneous activ...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/0378-5955(96)00020-2
更新日期：1996-05-01 00:00:00
abstract：:The mechanisms underlying the ototoxicity of ethacrynic acid (EA) are not fully understood. Previous studies have focused on morphologic and enzymatic changes in the stria vascularis. The current experiment shows that one of the earliest effects of EA is ischemia, resulting from impaired blood flow in vessels supplyin...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/s0378-5955(02)00585-3
更新日期：2002-11-01 00:00:00
abstract：:Hair cells of the lateral line system in fish may differ in their susceptibility to damage by aminoglycoside antibiotics. Gentamicin has been reported to damage hair cells within canal neuromasts, but not those within superficial neuromasts. This finding, based on SEM imaging, indicates a distinction in the physiology...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/j.heares.2010.01.001
更新日期：2010-03-01 00:00:00
abstract：:The introduction of foreign genes into cells has become an effective means of achieving intracellular expression of foreign proteins, both for therapeutic purposes and for experimental manipulation. Gene delivery to the nervous system has been extensively studied, primarily using viral vectors. However, to date less w...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/s0378-5955(99)00045-3
更新日期：1999-08-01 00:00:00
abstract：:Although pulmonary infections caused by Pseudomonas aeruginosa can hardly be eradicated in patients with cystic fibrosis (CF, the most common genetic disease among Caucasians), these patients are mainly treated with intravenous and nebulized tobramycin. Long-term treatment with tobramycin, however, may induce ototoxic...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/s0378-5955(97)00191-3
更新日期：1998-01-01 00:00:00
abstract：:Neural auditory thresholds in the guinea pig can be temporarily improved by up to 6 dB about 2 min after the cessation of an moderately intense low-frequency tone (Kirk and Patuzzi, 1997). We have measured changes in the f2-f1 distortion product otoacoustic emission (DPOAE) and low-frequency microphonic potential in s...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/s0378-5955(97)00104-4
更新日期：1997-10-01 00:00:00
abstract：:This study is the continuation of the functional probing of the auditory periphery in the normal and jaundiced rat. Threshold tuning curves from normal rat auditory nerve fibers were comparable to those reported in other mammals. Life-long unconjugated hyperbilirubinemia does not appear to have a widespread, demonstra...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/0378-5955(91)90139-z
更新日期：1991-07-01 00:00:00
abstract：:Progress in drug delivery to the ear has been achieved over the last few years. This review illustrates the main mechanisms of controlled drug release and the resulting geometry- and size-dependent release kinetics. The potency, physicochemical properties, and stability of the drug molecules are key parameters for des...
journal_title：Hearing research
pub_type： 杂志文章,评审
doi：10.1016/j.heares.2018.03.006
更新日期：2018-10-01 00:00:00
abstract：:This study addressed the hypotheses that the growth of the level of distortion product otoacoustic emissions (LDP) with primary-tone level reflects the behavior of a third-order nonlinear polynomial system, and that two sources exist for these distortion products. The results indicated that the 2f1-f2 otoacoustic emis...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/0378-5955(93)90016-t
更新日期：1993-12-01 00:00:00
abstract：:Age pigment in the sensory and supporting cells was a prominent characteristic distinguishing old saccules from young. However, the pigment was not distributed uniformly throughout the sensory epithelium but displayed cell-specific patterns of accumulation. The highest cytoplasmic volume density was in the old support...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/0378-5955(89)90038-5
更新日期：1989-01-01 00:00:00
abstract：:Exposure of the vestibulo-cochlear anastomosis in the cat allows single-unit recording of afferent fibers originating from inner hair cells and olivocochlear efferent fibers to the outer hair cells. Comparison of data obtained from individual animals show similarities in absolute threshold and dynamic range between th...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/0378-5955(88)90105-0
更新日期：1988-07-15 00:00:00
abstract：:We determined velocity discrimination thresholds and Weber fractions for sounds revolving around the listener at very high velocities. Sounds used were a broadband white noise and two harmonic sounds with fundamental frequencies of 330 Hz and 1760 Hz. Experiment 1 used velocities ranging between 288°/s and 720°/s in a...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/j.heares.2014.07.014
更新日期：2014-10-01 00:00:00
abstract：:C57BL/6 inbred mice are frequently used as models in auditory research, mostly the C57BL/6J and C57BL/6N substrains. Genetic variation and phenotypic disparities between these two substrains have been extensively investigated, but conflicting information exists about differences in their auditory and vestibular phenot...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/j.heares.2014.10.005
更新日期：2014-12-01 00:00:00
abstract：:In the surgical treatment of otosclerosis, the coupling between the stapes prosthesis and the long process of the incus is critical. After surgery, connective tissue and mucosa may grow over the coupling area and thereby influence the sound transmission properties of the incus-prosthesis interface. It was the hypothes...
journal_title：Hearing research
pub_type： 杂志文章
doi：10.1016/j.heares.2009.08.012
更新日期：2010-05-01 00:00:00
