WASHINGTON: Researchers explain how precision genome editing tools have enabled precision gene correction and disease rescue in hereditary retinal diseases (IRDs).
The paper describes recent preclinical achievements and clinical approaches to genome editing for the treatment of hereditary degenerative retinal diseases and emphasizes that there is hope that in vivo gene editing will be the future treatment paradigm for IRDs.
There are currently no effective treatments for these devastating diseases that often lead to blindness. “Genome editing technologies are an excellent approach to address the root causes of genetic disorders,” said Dr. Krzysztof Palczewski, Donald Bren Professor of Ophthalmology at the UCI School of Medicine and corresponding author.
“Technologies in genome editing have continually evolved to enable precise genome editing with fewer side effects and risks, making precise genome editing possible.”
The paper describes advances in using genome editing to treat IRDs and important considerations for robust clinical translation.
“More and more CRISPR-based treatment approaches are being tested in clinical trials,” says Palczewski. “We believe that there will be an increasing number of clinical trials targeting IRDs and that any mutation that causes them will be amenable to treatment with this approach.”
Programmable CRISPR-Cas nucleases are powerful tools for gene disruption, but they are ill-suited for precisely correcting pathogenic mutations in most therapeutic settings. Improvements are needed for clinical translation.
Hereditary retinal diseases (IRDs) are a genetically heterogeneous group of blinding diseases characterized by progressive degeneration of the photoreceptors as well as the retinal pigment epithelium (RPE). These disorders affect 1 in 3,000 people worldwide and significantly impact patients’ quality of life.
IRDs are caused by mutations in genes critical to retinal or RPE development and/or function, and more than 270 causative genes have been identified.
In the last two decades, major advances in gene therapy have raised new hopes for successful treatment of these IRDs. Recently, precision genome editing tools developed by The Liu Lab, including Base Editors (BEs) and Prime Editors (PEs), have enabled efficient and precise target gene correction instead of gene disruption in various therapeutic settings, including mouse models, including IRDs.
Precise target gene editing greatly expands the potential therapeutic applications of genome editing technologies, since most genetic disorders cannot be treated by gene disruption.
“Precision medicine for IRDs has promising prospects as basic research has consistently led to the development of therapeutic tools to target patient-specific genetic mutations,” said Palczewski.
“The results of the first clinical trials using in vivo gene editing to treat IRDs will be crucial for the development and implementation of future precise genome editing therapies.”