In vivo gene editing for treatment of congenital blindness Editas announces results of first human trial

Today, Editas Medicine announced the preliminary data of its in vivo gene editing therapy EDIT-101, a phase 1/2 clinical trial for the treatment of Leber congenital amaurosis 10 (LCA10)

Congenital amaurosis (LCA) is a type of hereditary retinal degenerative disease, which is the most common cause of hereditary blindness in children

EDIT-101 loads the gene encoding the Cas9 nuclease variant SaCas9 and two guide RNAs (gRNA) into the AAV5 vector, and delivers the gene editing system to the photoreceptor cells by subretinal injection

▲The mechanism of action of EDIT-101 (picture source: Editas Medicine official website)

Safety and efficacy results of EDIT-101

In this clinical trial, a total of 6 adult LCA10 patients have received different doses of EDIT-101 (two low doses and four medium doses)

It is worth mentioning that the study did not find the production of antibodies against Cas9

Based on these positive results, the independent data monitoring committee has allowed this clinical trial to enroll pediatric patients to receive medium-dose EDIT-101 treatment

In terms of the evaluation of the efficacy of EDIT-101, this trial used three tests to detect visual function to test the patient's visual acuity (BCVA), light sensitivity (FST), and visual navigation ability

The test results showed that of the 4 patients who received the middle dose of EDIT-101, one patient's visual function improved in all three tests, and the function improvement lasted for at least 6 months

▲The visual function changes of a patient treated with a medium dose of EDIT-101 (Image source: Editas Medicine official website)

Another patient who received medium-dose treatment showed signs of clinical activity in the photosensitivity test after receiving the treatment for 3 months.

Views of external experts

Regarding this result, external experts said that the lack of efficacy in low-dose treatment patients is not an unexpected result.

This means that the results of patients receiving high-dose EDIT-101 treatment will be more concerned

Fyodor Urnov, a professor of molecular biology at the University of California, Berkeley, pointed out that because this therapy edits photoreceptor cells in the retina, researchers cannot determine the efficiency of gene editing through routine tissue biopsies, and they can only use other alternative endpoints

"As far as I know, these data provide the first case for answering a critical safety question, that is, will CRISPR therapy stimulate an immune response and prevent patients from receiving other CRISPR therapies in the future?" Professor Urnov said, "Currently The data is positive

At the same time, Professors Komor and Urnov said that the continued follow-up of patients treated with low and medium doses is crucial, because safety signals related to gene editing and gene therapy may appear unexpectedly several years after receiving treatment

Look to the future

Since its inception, CRISPR gene editing technology has made rapid progress not only in the field of basic research, but also in clinical development

In June of this year, the in vivo editing therapy jointly developed by Intellia Therapeutics and Regeneron achieved positive results in a phase 1 clinical trial.

This field has also received increasing attention from pharmaceutical companies and capital.
Recently, Mammoth Biosciences, co-founded by Nobel laureate Dr.
Jennifer Doudna, completed nearly 200 million US dollars in financing, and will focus on the development of in vivo gene editing therapies with permanent healing potential
.
Moderna has established Moderna Genomics to use its expertise in mRNA and lipid nanoparticle technology to perform large-scale and complex genome editing
.

It is true that there are still multiple challenges in gene editing in the human body, delivery and safety of therapies
.
However, new scientific discoveries in this field are also endless.
Recently, many research institutions have discovered Cas enzymes with smaller molecular weights and new proteases with gene editing capabilities, providing new tools for solving the challenges of gene editing system delivery
.

Reference materials:

[1] Editas Medicine Announces Positive Initial Clinical Data from Ongoing Phase 1/2 BRILLIANCE Clinical Trial of EDIT-101 for LCA10.
Retrieved September 29, 2021, from https:// /29/2305445/0/en/Editas-Medicine-Announces-Positive-Initial-Clinical-Data-from-Ongoing-Phase-1-2-BRILLIANCE-Clinical-Trial-of-EDIT-101-for-LCA10.
html

[2] BRILLIANCE: A Phase 1/2 Single Ascending Dose Study of EDIT-101, an in vivo CRISPR Gene Editing Therapy in CEP290-Related Retinal Degeneration.
Retrieved September 29, 2021, from https://editasmedicine.
gcs-web.
com/static-files/22b32d3d-e38f-4e90-899c-a2e701872745

[3] Editas CRISPR treatment improved vision for one patient, but not others, early data show.
Retrieved September 29, 2021, from https:// -a-signal-of-vision-improvement-but-more-needed/

[4] Editas' CRISPR-based eye therapy proves safe, but the jury's still out on whether it works.
Retrieved September 29, 2021, from https://endpts.
com/editas-crispr-based-eye-therapy-proves- safe-but-the-jurys-still-out-on-whether-it-works/