A5000403069- Retinal Development and Disorders
- Hearing, Cochlea, Tinnitus, Genetics
- RNA regulation and disease
- Sirtuins and Resveratrol in Medicine
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Hearing Loss and Rehabilitation
- Retinal and Macular Surgery
- Bacteriophages and microbial interactions
- Photoreceptor and optogenetics research
- Pluripotent Stem Cells Research
- Peroxisome Proliferator-Activated Receptors
- Synthesis and Characterization of Heterocyclic Compounds
- Genomics, phytochemicals, and oxidative stress
- RNA Research and Splicing
- Photochromic and Fluorescence Chemistry
- Ocular Disorders and Treatments
- Bacterial biofilms and quorum sensing
- Microbial Community Ecology and Physiology
- Nerve injury and regeneration
- Retinal Diseases and Treatments
- RNA modifications and cancer
- Animal Genetics and Reproduction
- Neuroscience and Neural Engineering
- Machine Learning in Bioinformatics
Penn Presbyterian Medical Center
2016-2022
University of Pennsylvania
2016-2022
Star Center
2020
National Institutes of Health
2013-2015
National Institute on Deafness and Other Communication Disorders
2013-2014
University of Southern Mississippi
2011
Abstract Adeno-associated virus (AAV) has been successfully used to deliver gene therapy improve auditory function in mouse models of hereditary hearing loss. Many forms loss have mutations which affect the cochlear hair cells, mechanosensory cells allow for sound detection and processing. While most conventional AAVs infect inner (IHCs) with various efficiencies, they outer (OHCs) supporting at lower levels cochlea. Here we examine infection patterns two synthetic (AAV2.7m8 AAV8BP2) ear....
Objectives/Hypothesis Gene therapy offers the possibility of delivering corrective genetic materials to cochlea, potentially improving hearing. In animals, most commonly used surgical methods for viral gene delivery cochlea are round window and cochleostomy approaches. However, patterns infection effects on hearing have not been directly compared between these two this study, we compare cochlear approaches using adeno‐associated virus serotype 2/8 (AAV8) as vehicle. Study Design Animal study...
Glaucoma is a group of progressive optic neuropathies that share common biological and clinical characteristics including irreversible changes to the nerve visual field loss caused by death retinal ganglion cells (RGCs). The RGCs manifests as characteristic cupping or degeneration, resulting in patients with Glaucoma. Published studies on vitro RGC differentiation from stem utilized classical signaling pathways mimicking development vivo. Although many strategies allowed for generation RGCs,...
Optic neuritis is a condition defined by autoimmune-mediated demyelination of the optic nerve and death retinal ganglion cells. SIRT1 NRF2 stimulate anti-inflammatory mechanisms have previously demonstrated therapeutic value in preclinical models neurodegenerative disease. Here we investigated neuroprotective potential or gene transfer using adeno-associated virus (AAV) vectors experimental autoimmune encephalomyelitis (EAE) model multiple sclerosis.C57Bl/6J mice were administered...
Abstract SIRT1 prevents retinal ganglion cell (RGC) loss in models of optic neuropathy following pharmacologic activation or genetic overexpression. The exact mechanism is not known, prior evidence suggests this through oxidative stress to either neighboring cells RGC specifically. We investigated the neuroprotective potential RGC-selective gene therapy nerve crush (ONC) model. hypothesized that AAV-mediated overexpression RGCs reduces loss, thereby preserving visual function. Cohorts...
Optic neuritis (ON), the most common ocular manifestation of multiple sclerosis, is an autoimmune inflammatory demyelinating disease also characterized by degeneration retinal ganglion cells (RGCs) and their axons, which commonly leads to visual impairment despite attempted treatments. Although ON etiology not known, changes in redox system exacerbated optic nerve inflammation play a major role pathogenesis disease. Silent information regulator 1 (sirtuin-1/SIRT1) ubiquitously expressed...
Ocular gene therapy with recombinant adeno-associated virus (AAV) has shown vector-mediated augmentation to be safe and efficacious in the retina one set of diseases (retinitis pigmentosa Leber congenital amaurosis (LCA) caused by RPE65 deficiency), excellent safety profiles date potential for efficacy several additional diseases. However, size constraints imposed packaging capacity AAV genome restrict application coding sequence lengths that are less than 5,000 nt. The most prevalent...
Patients with Zellweger spectrum disorder (ZSD) commonly present vision loss due to mutations in PEX genes required for peroxisome assembly and function. Here, we evaluate PEX1 retinal gene augmentation therapy a mouse model of mild ZSD bearing the murine equivalent (PEX1-p[Gly844Asp]) most common human mutation. Experimental adeno-associated virus 8.cytomegalovirus.human PEX1.hemagglutinin (AAV8.CMV.HsPEX1.HA) control AAV8.CMV.EGFP vectors were administered by subretinal injection...
Validation of gene transfer vectors containing tissue-specific promoters in cell-based functional assays poses a formidable challenge for therapy product development. Here, we describe novel approach based on CRISPR/dCas9 transcriptional activation to achieve robust transgene expression from cassettes tissue or cell type-specific after infection with AAV systems. Guide RNA sequences targeting two that are highly active within mammalian photoreceptors were screened promoter assay. Using this...
Mutations within over 250 known genes are associated with inherited retinal degeneration. Clinical success following gene-replacement therapy for congenital blindness due to RPE65 mutations establishes a platform the development of downstream treatments targeting other forms ocular disease. Unfortunately, several challenges relevant complex disease pathology and limitations current gene-transfer technologies impede related strategies each specific form Here, we describe gene-augmentation...
No AccessPerspectives on Hearing and Disorders: Research DiagnosticsArticle1 May 2013Gene Therapy for Hereditary Loss Devin S. McDougald, Lisa L. Cunningham Wade W. Chien McDougald National Institute Deafness Other Communication Disorders, Institutes of HealthRockville, MD Google Scholar More articles by this author , Disorders (NIDCD), Health (NIH), received funding the work article from NIDCD, Division Intramural https://doi.org/10.1044/hhd17.1.5 SectionsAboutFull TextPDF ToolsAdd to...
Abstract Glaucoma is a group of progressive optic neuropathies that share common biological and clinical characteristics including irreversible changes to the nerve visual field loss caused by death retinal ganglion cells (RGCs). The RGCs manifests as characteristic cupping or degeneration, resulting in patients with Glaucoma. Published studies on vitro RGC differentiation from stem utilized classical signaling pathways mimicking development vivo . Although many strategies allowed for...