Abstract
Recently, there have been revolutions in the development of both gene medicine therapy and genome surgical treatments for inherited disorders. Much of this progress has been centered on hereditary retinal dystrophies, because the eye is an immune-privileged and anatomically ideal target. Gene therapy treatments, already demonstrated to be safe and efficacious in numerous clinical trials, are benefitting from the development of new viral vectors, such as dual and triple adeno-associated virus (AAV) vectors. CRISPR/Cas9, which revolutionized the field of gene editing, is being adapted into more precise “high fidelity” and catalytically dead variants. Newer CRISPR endonucleases, such as CjCas9 and Cas12a, are generating excitement in the field as well. Stem cell therapy has emerged as a promising alternative, allowing human embryo-derived stem cells and induced pluripotent stem cells to be edited precisely in vitro and then reintroduced into the body. This article highlights recent progress made in gene therapy and genome surgery for retinal disorders, and it provides an update on precision medicine Food and Drug Administration (FDA) treatment trials.
Highlights
With the rising mean age of the human population and rapid advances in conventional medicine, we are seeing an increase in the number of diseases that take root not from environmental factors, but from the human genome itself
Cas9 requires tracrRNA to process crRNA, but Cas12a exhibits ribonuclease activity that enables its precursor crRNA to be processed into mature crRNA. This shorter crRNA used by Cas12a, measuring around 42 nucleotides, is cheaper to design and easier to deliver than the longer sgRNA sequence used by Cas9, which measures around 100 nt [29]
A third option is the use of mesenchymal stem cells (MSCs), multipotent cells that are found in various adult tissues and have been shown to be able to differentiate into a variety of retinal cell types, including retinal pigment epithelium (RPE), PR, bipolar, amacrine, and Müller glial cells
Summary
With the rising mean age of the human population and rapid advances in conventional medicine, we are seeing an increase in the number of diseases that take root not from environmental factors, but from the human genome itself. To address this issue, gene therapy has risen to prominence in the field of translational research. Leber congenital amaurosis (LCA) proved the efficacy of retinal gene therapy [9,10] These successes, along with the recent, promising advent of clustered regularly interspaced short palindromic repeats (CRISPR)-driven genome surgery, have accelerated research in the field. This article will review current and developing methods of genome surgery and genetic medicine therapy, as well as recent applications in disease-specific clinical trials
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
