Gene and Cell Therapy for Inherited Retinal Dystrophies

Abstract

Gene therapy and cell therapy are intersecting fields of biomedical research with the common aim of repairing the direct causes or consequences of genetic diseases by using genes and cells, respectively. Gene therapy is broadly defined as a set of strategies that modify the expression of an individual's genes for therapeutic benefit. It requires the administration of a specific deoxyribonucleic acid (DNA) (or ribonucleic acid (RNA)) into the patient's cells. Cell therapy on the other hand requires administration of a population of intact live cells to a patient whose cells have been lost due to injury or disease. These emerging strategies can also be applied in acquired diseases in order to re‐establish equilibrium and halt disease progression. In some cases, gene and cell therapy may be combined in order to obtain a therapeutic effect. In addition to becoming emerging therapeutics in the clinic, these two fields of research continually generate tools, concepts and techniques for elucidating biological questions across multiple disciplines. Key Concepts The retina lines the back of the eye and comprises six different types of neuronal cells and their underlying retinal pigment epithelium (RPE). Photoreceptors are the light‐sensitive first‐order neurons of the retina which capture the light stimulus and transform it into an electric signal. Human iPSC have the same features of hESC in terms of their differentiation capacity. Gene therapy is the use of genetic material as a drug to treat a chronic condition.

AAV-Mediated Gene Delivery to 3D Retinal Organoids Derived from Human Induced Pluripotent Stem Cells

“…Widespread utility of AAV in clinical studies and the distinct transduction profiles of various AAV serotypes in different species stresses the importance of evaluating AAV vector efficiency in a more relevant human model. Human retinal organoids derived from hiPSC have proven useful not only for cell replacement strategies, but also for drug screening, disease modelling, gene correction and recently, optogenetic screening and subcellular trafficking [12,32]. Moreover, with genome editing gaining momentum as a therapeutic modality, gene-editing tools also require testing in human organoids.…”

Control of Microbial Opsin Expression in Stem Cell Derived Cones for Improved Outcomes in Cell Therapy

“…The ability to genetically modify retinal organoids is essential for their utility as disease models as well as their therapeutic use for regenerative medicine. Genetic modification is a powerful tool that allows for the introduction of alterations ranging from small changes in the genome to the removal or integration of entire genes to the expression of exogenous genes to control cellular function (Garita-Hernandez et al, 2016 ). This enables researchers to investigate individual genes relating to cellular functions, and interactions.…”