Emerging Gene Therapies for Genetic Hearing Loss

Translational issues in cochlear synaptopathy

(2017) Ann E. Hickox et al.   HEARING RESEARCH

Noise-induced cochlear synaptopathy: Past findings and future studies

(2017) Megan Kobel et al.   HEARING RESEARCH

Gene Therapy Restores Balance and Auditory Functions in a Mouse Model of Usher Syndrome

(2017) Kevin Isgrig et al.   MOLECULAR THERAPY

Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV

(2017) Bence György et al.   MOLECULAR THERAPY

Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c

(2017) Bifeng Pan et al.   NATURE BIOTECHNOLOGY

A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear

(2017) Lukas D Landegger et al.   NATURE BIOTECHNOLOGY

Cochlear gene therapy with ancestral AAV in adult mice: complete transduction of inner hair cells without cochlear dysfunction

(2017) Jun Suzuki et al.   Scientific Reports

RNA Interference Prevents Autosomal-Dominant Hearing Loss

(2016) Seiji B. Shibata et al.   AMERICAN JOURNAL OF HUMAN GENETICS

Methionine Sulfoxide Reductase B3-Targeted In Utero Gene Therapy Rescues Hearing Function in a Mouse Model of Congenital Sensorineural Hearing Loss

(2016) Min-A Kim et al.   ANTIOXIDANTS & REDOX SIGNALING

Single point mutation in adeno-associated viral vectors -DJ capsid leads to improvement for gene delivery in vivo

(2016) Yingying Mao et al.   BMC BIOTECHNOLOGY

Genetic causes of moderate to severe hearing loss point to modifiers

(2016) S. Naz et al.   CLINICAL GENETICS

Single residue AAV capsid mutation improves transduction of photoreceptors in the Abca4 −/− mouse and bipolar cells in the rd1 mouse and human retina ex vivo

(2016) S R De Silva et al.   GENE THERAPY

Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss

(2016) Christina M. Sloan-Heggen et al.   HUMAN GENETICS

Targeted epigenetic repression of a lymphoma oncogene by sequence-specific histone modifiers induces apoptosis in DLBCL

(2016) Hong Luo et al.   LEUKEMIA & LYMPHOMA

Structural Basis for the Altered PAM Specificities of Engineered CRISPR-Cas9

(2016) Seiichi Hirano et al.   MOLECULAR CELL

Gene Therapy Restores Hair Cell Stereocilia Morphology in Inner Ears of Deaf Whirler Mice

(2016) Wade W Chien et al.   MOLECULAR THERAPY

Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage

(2016) Alexis C. Komor et al.   NATURE

A small molecule mitigates hearing loss in a mouse model of Usher syndrome III

(2016) Kumar N Alagramam et al.   Nature Chemical Biology

Recessive mutations of TMC1 associated with moderate to severe hearing loss

(2016) Ayesha Imtiaz et al.   NEUROGENETICS

The delivery of therapeutic oligonucleotides

(2016) Rudolph L. Juliano   NUCLEIC ACIDS RESEARCH

Alternative Splice Forms Influence Functions of Whirlin in Mechanosensory Hair Cell Stereocilia

(2016) Seham Ebrahim et al.   Cell Reports

A Comprehensive Review on Exosomes and Microvesicles as Epigenetic Factors

(2016) Behnaz Bakhshandeh et al.   Current Stem Cell Research & Therapy

Adenovirus Vectors Target Several Cell Subtypes of Mammalian Inner Ear In Vivo

(2016) Yilai Shu et al.   NEURAL PLASTICITY

Reprogrammable CRISPR/Cas9-based system for inducing site-specific DNA methylation

(2016) James I. McDonald et al.   Biology Open

Multilineage transduction of resident lung cells in vivo by AAV2/8 for α1-antitrypsin gene therapy

(2016) Julia G Payne et al.   Molecular Therapy-Methods & Clinical Development

Gene Therapy for Sensorineural Hearing Loss

(2015) Wade W. Chien et al.   EAR AND HEARING

Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange‐Nielsen deafness syndrome

(2015) Qing Chang et al.   EMBO Molecular Medicine

Potential treatments for genetic hearing loss in humans: current conundrums

(2015) R Minoda et al.   GENE THERAPY

Development of novel AAV serotype 6 based vectors with selective tropism for human cancer cells

(2015) R Sayroo et al.   GENE THERAPY

The application of genome editing in studying hearing loss

(2015) Bing Zou et al.   HEARING RESEARCH

Perinatal Gjb2 gene transfer rescues hearing in a mouse model of hereditary deafness

(2015) T. Iizuka et al.   HUMAN MOLECULAR GENETICS

Zebrafish Models for the Mechanosensory Hair Cell Dysfunction in Usher Syndrome 3 Reveal That Clarin-1 Is an Essential Hair Bundle Protein

(2015) S. R. Gopal et al.   JOURNAL OF NEUROSCIENCE

Linear polyethylenimine-plasmid DNA nanoparticles are ototoxic to the cultured sensory epithelium of neonatal mice

(2015) HAN ZHOU et al.   Molecular Medicine Reports

Engineered CRISPR-Cas9 nucleases with altered PAM specificities

(2015) Benjamin P. Kleinstiver et al.   NATURE

Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition

(2015) Benjamin P Kleinstiver et al.   NATURE BIOTECHNOLOGY

Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements

(2015) Pratiksha I Thakore et al.   NATURE METHODS

Development of an intein-mediated split–Cas9 system for gene therapy

(2015) Dong-Jiunn Jeffery Truong et al.   NUCLEIC ACIDS RESEARCH

Tmc gene therapy restores auditory function in deaf mice

(2015) Charles Askew et al.   Science Translational Medicine

Trans-spliced Cas9 allows cleavage of HBB and CCR5 genes in human cells using compact expression cassettes

(2015) Eli J. Fine et al.   Scientific Reports

TMC1 and TMC2 Localize at the Site of Mechanotransduction in Mammalian Inner Ear Hair Cell Stereocilia

(2015) Kiyoto Kurima et al.   Cell Reports

In Silico Reconstruction of the Viral Evolutionary Lineage Yields a Potent Gene Therapy Vector

(2015) Eric Zinn et al.   Cell Reports

Ototoxicity-induced loss of hearing and inner hair cells is attenuated by HSP70 gene transfer

(2015) Yohei Takada et al.   Molecular Therapy-Methods & Clinical Development

Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles

(2014) Marina Colombo et al.   Annual Review of Cell and Developmental Biology

Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis

(2014) Sonia A. Melo et al.   CANCER CELL

Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation

(2014) Luke A. Gilbert et al.   CELL

Efficient gene delivery to the cone-enriched pig retina by dual AAV vectors

(2014) P Colella et al.   GENE THERAPY

The Neutral Sphingomyelinase Pathway Regulates Packaging of the Prion Protein into Exosomes

(2014) Belinda B. Guo et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Whirlin and PDZ Domain-containing 7 (PDZD7) Proteins Are Both Required to Form the Quaternary Protein Complex Associated with Usher Syndrome Type 2

(2014) Qian Chen et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Optimizing atoh1-induced vestibular hair cell regeneration

(2014) Hinrich Staecker et al.   LARYNGOSCOPE

Tropism-modified AAV Vectors Overcome Barriers to Successful Cutaneous Therapy

(2014) Jessica Sallach et al.   MOLECULAR THERAPY

Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo

(2014) John A Zuris et al.   NATURE BIOTECHNOLOGY

Development of a cell-based treatment for long-term neurotrophin expression and spiral ganglion neuron survival

(2014) M.P. Zanin et al.   NEUROSCIENCE

MegaTevs: single-chain dual nucleases for efficient gene disruption

(2014) Jason M. Wolfs et al.   NUCLEIC ACIDS RESEARCH

Identification of the endosomal sorting complex required for transport-I (ESCRT-I) as an important modulator of anti-miR uptake by cancer cells

(2014) Timothy R. Wagenaar et al.   NUCLEIC ACIDS RESEARCH

A Novel DFNA36 Mutation in TMC1 Orthologous to the Beethoven (Bth) Mouse Associated with Autosomal Dominant Hearing Loss in a Chinese Family

(2014) Yali Zhao et al.   PLoS One

Sound Strategies for Hearing Restoration

(2014) G. S. G. Geleoc et al.   SCIENCE

Close-Field Electroporation Gene Delivery Using the Cochlear Implant Electrode Array Enhances the Bionic Ear

(2014) J. L. Pinyon et al.   Science Translational Medicine

Dual Adeno-Associated Virus Vectors Result in Efficient In Vitro and In Vivo Expression of an Oversized Gene, MYO7A

(2014) Frank M. Dyka et al.   Human Gene Therapy Methods

Efficient Production of Dual Recombinant Adeno-Associated Viral Vectors for Factor VIII Delivery

(2014) Qizhao Wang et al.   Human Gene Therapy Methods

Recent advances in in vivo applications of intein-mediated protein splicing

(2014) Natalya I Topilina et al.   Mobile DNA

Effect of lentiviruses carrying enhanced green fluorescent protein injected into the scala media through a cochleostomy in rats

(2013) Yan Wei et al.   AMERICAN JOURNAL OF OTOLARYNGOLOGY

Immune responses to AAV vectors: overcoming barriers to successful gene therapy

(2013) F. Mingozzi et al.   BLOOD

Integration-deficient lentivectors: an effective strategy to purify and differentiate human embryonic stem cell-derived hepatic progenitors

(2013) Guanghua Yang et al.   BMC BIOLOGY

Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression

(2013) Lei S. Qi et al.   CELL

Effective delivery of large genes to the retina by dual AAV vectors

(2013) Ivana Trapani et al.   EMBO Molecular Medicine

Gene therapy for deafness

(2013) D C Kohrman et al.   GENE THERAPY

Virally expressed connexin26 restores gap junction function in the cochlea of conditional Gjb2 knockout mice

(2013) Q Yu et al.   GENE THERAPY

Triple Trans-Splicing Adeno-Associated Virus Vectors Capable of Transferring the Coding Sequence for Full-Length Dystrophin Protein into Dystrophic Mice

(2013) Taeyoung Koo et al.   HUMAN GENE THERAPY

Round window membrane intracochlear drug delivery enhanced by induced advection

(2013) David A. Borkholder et al.   JOURNAL OF CONTROLLED RELEASE

Early postnatal virus inoculation into the scala media achieved extensive expression of exogenous green fluorescent protein in the inner ear and preserved auditory brainstem response thresholds

(2013) Yunfeng Wang et al.   JOURNAL OF GENE MEDICINE

Gene therapy clinical trials worldwide to 2012 - an update

(2013) Samantha L. Ginn et al.   JOURNAL OF GENE MEDICINE

TALENs: Customizable Molecular DNA Scissors for Genome Engineering of Plants

(2013) Kunling Chen et al.   Journal of Genetics and Genomics

Harmonin enhances voltage-dependent facilitation of Cav1.3 channels and synchronous exocytosis in mouse inner hair cells

(2013) Frederick D. Gregory et al.   JOURNAL OF PHYSIOLOGY-LONDON

Rescue of hearing and vestibular function by antisense oligonucleotides in a mouse model of human deafness

(2013) Jennifer J Lentz et al.   NATURE MEDICINE

Correction of the Middle Eastern M712T Mutation Causing GNE Myopathy by Trans-Splicing

(2013) Tzukit Tal-Goldberg et al.   NEUROMOLECULAR MEDICINE

TMC1 and TMC2 Are Components of the Mechanotransduction Channel in Hair Cells of the Mammalian Inner Ear

(2013) Bifeng Pan et al.   NEURON

Ectopic hair cell-like cell induction by Math1 mainly involves direct transdifferentiation in neonatal mammalian cochlea

(2013) Juanmei Yang et al.   NEUROSCIENCE LETTERS

Analysis of Transduction Efficiency, Tropism and Axonal Transport of AAV Serotypes 1, 2, 5, 6, 8 and 9 in the Mouse Brain

(2013) Dominik F. Aschauer et al.   PLoS One

Inner ear supporting cells: Rethinking the silent majority

(2013) Guoqiang Wan et al.   SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY

Cotransfection of Pax2 and Math1 promote in situ cochlear hair cell regeneration after neomycin insult

(2013) Yan Chen et al.   Scientific Reports

An Independent Construct for Conditional Expression of Atonal Homolog-1

(2013) Mark A. Parker et al.   Human Gene Therapy Methods

Humoral Immune Response to AAV

(2013) Roberto Calcedo et al.   Frontiers in Immunology

Gene transfer in inner ear cells: a challenging race

(2012) R Sacheli et al.   GENE THERAPY

Gene therapy for the inner ear

(2012) Hideto Fukui et al.   HEARING RESEARCH

An AAV2/5 Vector Enhances Safety of Gene Transfer to the Mouse Salivary Gland

(2012) R.N. Geguchadze et al.   JOURNAL OF DENTAL RESEARCH

The Mechanosensory Structure of the Hair Cell Requires Clarin-1, a Protein Encoded by Usher Syndrome III Causative Gene

(2012) R. Geng et al.   JOURNAL OF NEUROSCIENCE

Restoration of Hearing in the VGLUT3 Knockout Mouse Using Virally Mediated Gene Therapy

(2012) Omar Akil et al.   NEURON

Regeneration of Stereocilia of Hair Cells by Forced Atoh1 Expression in the Adult Mammalian Cochlea

(2012) Shi-Ming Yang et al.   PLoS One

Monomeric site-specific nucleases for genome editing

(2012) B. P. Kleinstiver et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Drug Delivery to the Inner Ear: Strategies and Their Therapeutic Implications for Sensorineural Hearing Loss

(2012) Teresa Rivera et al.   Current Drug Delivery

Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations

(2011) Samuel G. Jacobson   ARCHIVES OF OPHTHALMOLOGY

Meganucleases and Other Tools for Targeted Genome Engineering: Perspectives and Challenges for Gene Therapy

(2011) George Silva et al.   CURRENT GENE THERAPY

The ESCRT Pathway

(2011) William M. Henne et al.   DEVELOPMENTAL CELL

Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear

(2011) L A Kilpatrick et al.   GENE THERAPY

Cochlear infrastructure for electrical hearing

(2011) Bryan E. Pfingst et al.   HEARING RESEARCH

Mechanotransduction in mouse inner ear hair cells requires transmembrane channel–like genes

(2011) Yoshiyuki Kawashima et al.   JOURNAL OF CLINICAL INVESTIGATION

Harmonin inhibits presynaptic Cav1.3 Ca2+ channels in mouse inner hair cells

(2011) Frederick D Gregory et al.   NATURE NEUROSCIENCE

The Discovery of Zinc Fingers and Their Applications in Gene Regulation and Genome Manipulation

(2010) Aaron Klug   Annual Review of Biochemistry

Math1 Gene Transfer Based on the Delivery System of Quaternized Chitosan/Na-Carboxymethyl-β-Cyclodextrin Nanoparticles

(2010) Li-Li Ren et al.   JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY

Sox2 Induces Neuronal Formation in the Developing Mammalian Cochlea

(2010) C. Puligilla et al.   JOURNAL OF NEUROSCIENCE

The structure of the harmonin/sans complex reveals an unexpected interaction mode of the two Usher syndrome proteins

(2010) J. Yan et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Mutation analysis of TMC1 identifies four new mutations and suggests an additional deafness gene at loci DFNA36 and DFNB7/11

(2009) N Hilgert et al.   CLINICAL GENETICS

A muscle-targeting peptide displayed on AAV2 improves muscle tropism on systemic delivery

(2009) C-Y Yu et al.   GENE THERAPY

Mutations in TMC1 contribute significantly to nonsyndromic autosomal recessive sensorineural hearing loss: A report of five novel mutations

(2009) Aslı Sırmacı et al.   INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY

Artificial exosomes as tools for basic and clinical immunology

(2009) Hugo De La Peña et al.   JOURNAL OF IMMUNOLOGICAL METHODS

Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial

(2009) Albert M Maguire et al.   LANCET

Integration-deficient Lentiviral Vectors: A Slow Coming of Age

(2009) Klaus Wanisch et al.   MOLECULAR THERAPY

Localization of inner hair cell mechanotransducer channels using high-speed calcium imaging

(2009) Maryline Beurg et al.   NATURE NEUROSCIENCE

Harmonin Mutations Cause Mechanotransduction Defects in Cochlear Hair Cells

(2009) Nicolas Grillet et al.   NEURON

Vision 1 Year after Gene Therapy for Leber's Congenital Amaurosis

(2009) Artur V. Cideciyan et al.   NEW ENGLAND JOURNAL OF MEDICINE

Gap Junctions

(2009) D. A. Goodenough et al.   Cold Spring Harbor Perspectives in Biology

HOX-GFP and WOX-GFP lentivirus vectors for inner ear gene transfer

(2008) Laura Pietola et al.   ACTA OTO-LARYNGOLOGICA

Impairment of SLC17A8 Encoding Vesicular Glutamate Transporter-3, VGLUT3, Underlies Nonsyndromic Deafness DFNA25 and Inner Hair Cell Dysfunction in Null Mice

(2008) Jérôme Ruel et al.   AMERICAN JOURNAL OF HUMAN GENETICS

A core cochlear phenotype in USH1 mouse mutants implicates fibrous links of the hair bundle in its cohesion, orientation and differential growth

(2008) G. Lefevre et al.   DEVELOPMENT

Expressionsmuster für nichtviral transfiziertes gfp in der Cochlea der Maus in vitro und in vivo

(2008) M. Praetorius et al.   HNO

Protein Trans-Splicing as a Means for Viral Vector-Mediated In Vivo Gene Therapy

(2008) Juan Li et al.   HUMAN GENE THERAPY

Gene transfer into guinea pig cochlea using adeno-associated virus vectors

(2008) Masaya Konishi et al.   JOURNAL OF GENE MEDICINE

Sensorineural Deafness and Seizures in Mice Lacking Vesicular Glutamate Transporter 3

(2008) Rebecca P. Seal et al.   NEURON