The Next Generation of Molecular and Cellular Therapeutics for Inherited Retinal Disease. 2021

Luis A Martinez Velazquez, and Brian G Ballios
Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA.

Inherited retinal degenerations (IRDs) are a diverse group of conditions that are often characterized by the loss of photoreceptors and blindness. Recent innovations in molecular biology and genomics have allowed us to identify the causative defects behind these dystrophies and to design therapeutics that target specific mechanisms of retinal disease. Recently, the FDA approved the first in vivo gene therapy for one of these hereditary blinding conditions. Current clinical trials are exploring new therapies that could provide treatment for a growing number of retinal dystrophies. While the field has had early success with gene augmentation strategies for treating retinal disease based on loss-of-function mutations, many novel approaches hold the promise of offering therapies that span the full spectrum of causative mutations and mechanisms. Here, we provide a comprehensive review of the approaches currently in development including a discussion of retinal neuroprotection, gene therapies (gene augmentation, gene editing, RNA modification, optogenetics), and regenerative stem or precursor cell-based therapies. Our review focuses on technologies that are being developed for clinical translation or are in active clinical trials and discusses the advantages and limitations for each approach.

UI MeSH Term Description Entries
D012162 Retinal Degeneration A retrogressive pathological change in the retina, focal or generalized, caused by genetic defects, inflammation, trauma, vascular disease, or aging. Degeneration affecting predominantly the macula lutea of the retina is MACULAR DEGENERATION. (Newell, Ophthalmology: Principles and Concepts, 7th ed, p304) Degeneration, Retinal,Degenerations, Retinal,Retinal Degenerations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000066829 Neuroprotection The physiological processes and techniques used by the body to prevent neuronal injury and degeneration in the central nervous system following acute disorders or as a result of chronic neurodegenerative diseases. Neural Protection,Neuron Protection,Neuronal Protection,Protection, Neural,Protection, Neuron,Protection, Neuronal
D000072669 Gene Editing Genetic engineering or molecular biology techniques that involve DNA REPAIR mechanisms for incorporating site-specific modifications into a cell's genome. Base Editing,Genome Editing,Editing, Base,Editing, Gene,Editing, Genome
D015316 Genetic Therapy Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions. Gene Therapy,Somatic Gene Therapy,DNA Therapy,Gene Therapy, Somatic,Genetic Therapy, Gametic,Genetic Therapy, Somatic,Therapy, DNA,Therapy, Gene,Therapy, Somatic Gene,Gametic Genetic Therapies,Gametic Genetic Therapy,Genetic Therapies,Genetic Therapies, Gametic,Genetic Therapies, Somatic,Somatic Genetic Therapies,Somatic Genetic Therapy,Therapies, Gametic Genetic,Therapies, Genetic,Therapies, Somatic Genetic,Therapy, Gametic Genetic,Therapy, Genetic,Therapy, Somatic Genetic
D044968 Regenerative Medicine A field of medicine concerned with developing and using strategies aimed at repair or replacement of damaged, diseased, or metabolically deficient organs, tissues, and cells via TISSUE ENGINEERING; CELL TRANSPLANTATION; and ARTIFICIAL ORGANS and BIOARTIFICIAL ORGANS and tissues. Medicine, Regenerative,Medicines, Regenerative,Regenerative Medicines
D058990 Molecular Targeted Therapy Treatments with drugs which interact with or block synthesis of specific cellular components characteristic of the individual's disease in order to stop or interrupt the specific biochemical dysfunction involved in progression of the disease. Targeted Molecular Therapy,Molecular Targeted Therapies,Molecular Therapy, Targeted,Targeted Molecular Therapies,Targeted Therapy, Molecular,Therapy, Molecular Targeted,Therapy, Targeted Molecular
D062308 Optogenetics The combination of genetic and optical methods in controlling specific events with temporal precision in targeted cells of a functioning intact biological system. Optogenetic Techniques,Optogenetic,Optogenetic Technique,Technique, Optogenetic,Techniques, Optogenetic
D064987 Cell- and Tissue-Based Therapy Therapies that involve the TRANSPLANTATION of CELLS or TISSUES developed for the purpose of restoring the function of diseased or dysfunctional cells or tissues. Cell Therapy,Tissue Therapy,Therapy, Cell,Therapy, Tissue,Cell and Tissue Based Therapy

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