The potential of precise genome editing in the treatment of hereditary retinal diseases

In a new paper, researchers at the University of California, Irvine, explain how precision genome editors enable precise genetic correction and disease rescue
for genetic retinal diseases (IRDs).
The study, titled "Precision genome editing in the eye," was published this week in the Proceedings of the National Academy of Sciences
.

This paper describes current preclinical success and clinical genome editing approaches to the treatment of hereditary retinal degenerative diseases, and highlights the promise that gene editing in living organisms will be the therapeutic paradigm
for IRDs in the future.
Currently, there are no effective treatments for these devastating diseases, which often lead to blindness
.

Dr.
Krzysztof Palczewski explains: "Genome editing technology is an excellent way
to target the root causes of genetic diseases.
" He is the Donald Burren Professor of Ophthalmology at UCI School of Medicine and corresponding author
.
"Genome editing technology continues to evolve to enable precise genome editing with fewer side effects and risks, making precise genome editing possible
.
"

This paper describes the progress of using genome editing to treat IRDs and important considerations
for robust clinical translation.

"More and more CRISPR-based treatments are being tested in clinical trials," Palczewski said
.
"We believe that there will be more and more clinical trials targeting IRD, and any mutation that causes IRD can be treated
with this approach.
"

Programmable CRISPR-Cas nuclease is an effective tool for gene destruction, but in most therapeutic settings, they are not suitable for precisely correcting pathogenic mutations
.
Clinical translation needs to be improved
.

Hereditary retinal diseases (IRDs) are a group of inherited heterogeneous blinding diseases characterized by progressive degradation
of photoreceptors and retinitis pigment epithelium (RPE).
These diseases affect about 1 in 3,000 people worldwide and profoundly affect the quality of life of
patients.
IRDs are caused by mutations in genes that are critical to the development and/or function of the retina or RPE, and more than 270 pathogenic genes
have been identified.

Over the past 20 years, significant advances in gene therapy have brought new hope
for the successful treatment of these IRDs.
Recently, the precise genome editors developed by Liu's lab, including base editors (BEs) and element editors (PEs), enable efficient and precise targeted gene correction rather than gene destruction in a variety of therapeutic settings, including mouse IRDs models
.
Precise target gene correction greatly expands the potential therapeutic applications of genome editing technology, as most genetic diseases cannot be treated
by gene destruction.

Palczewski said: "Precision medicine for IRDs has a good prospect because basic science has been leading the development of therapeutic tools aimed at targeting patient-specific genetic mutations
.
" "The results of preliminary clinical trials suggest that gene editing therapies for IRDs in living organisms are critical
for the design and translation of future precision genome editing therapies.
"

This work was done in collaboration with David R.
Liu and was supported in part by the National Institutes of Health, the National Science Foundation, the Howard Hughes Medical Institute, and the Prevention of Blindness Research
.

essay

Precision genome editing in the eye