Let’s Chat About … CRISPR and Gene Editing

For the first time, early research data shows that a gene editing technique called CRISPR improved vision in people living with a form of Leber congenital amaurosis (LCA), according to Dr. Edmond Chen of Editas Medicine.

“It’s the first time anyone has demonstrated the potential of editing in human eyes,” Dr. Chen said. “We kind of dreamed about this since 2014.”

Researchers administered EDIT-101, an experimental CRISPR gene editing medicine, through a subretinal injection to reach and deliver the gene-editing machinery directly to the retina’s photoreceptor cells.

The research targets LCA10 caused by a mutation in the CEP290 gene, the most common of the more than 27 forms of LCA. 

Dr. Chen is the Vice President of Clinical Development at Editas Medicine, a gene editing company based in Cambridge, Mass. The company focuses on developing CRISPR-based treatments. 

CRISPR (pronounced “crisper”) is an acronym for Clustered, Regularly Interspaced, Short Palindromic Repeats. It refers to a recently developed gene editing technology that can revise, remove, and replace DNA in a highly targeted manner.

As part of our Hope in Focus webinar series, Dr. Chen described the early, but exciting, data from the ongoing Phase 1/2 Brilliance clinical trial of EDIT-101 in our October episode: “Let’s Chat About…CRISPR and gene-editing technology.”  Our Director of Marketing and Communications Elissa Bass moderated the session, which you can view here.

Dr. Chen oversees a portfolio spanning the therapeutic areas of hematology, oncology, ophthalmology, and neuroscience. As a physician executive with more than 20 years of combined clinical and industry experience, he has a track record of success at companies, including Merck and Bayer. 

His therapeutic area and drug development expertise is deep and diverse, from rare disease and indications such as bronchiectasis, vasculitis, and pulmonary hypertension, to large cardiovascular areas including congestive heart failure, thrombosis, and therapeutics for primary and secondary cardiovascular prevention. 

He earned his medical degree at the University of California, San Francisco School of Medicine, where he trained and practiced in internal medicine and cardiology. He holds a Bachelor of Arts with Honors in Molecular and Cell Biology, Neurobiology, from the University of California, Berkeley. 

Exciting early results for CRISPR 

Dr. Chen described his passion for innovation and his interest in developing life-saving treatments, including a new aspirin.

Then he thought to himself, “We probably don’t need another aspirin,” and pivoted this passion for innovation to life-altering research, including working with the CRISPR gene-editing treatment.

He has been with Editas since 2020; the company’s work on LCA10 began in 2014. 

Dr. Chen said he is excited about the first results of the clinical trial and added that the research is part of an ongoing, current investigation of which “we’re not making any claims.”

Editas recently released early results of the first six patients in the EDIT-101 Brilliance trial at the International Symposium on Retinal Degeneration. Efficacy results were limited to the first five patients treated with the low- to mid-doses and followed for at least three months. 

Two of the three patients treated with the mid-dose and followed for up to six months showed improved vision, results that suggest successful editing with EDIT-101. Patients will need to be treated and followed over time to ensure the safety and efficacy of the drug. EDIT-101 is now being assessed at a higher dose and in pediatric patients.

Editas currently is recruiting for children, ages 3 to 17. For recruitment information, contact Editas Medicine’s Clinical Trial Team at 617-401-9007 or patients@editasmed.com. For more information, go to clinicaltrials.gov NCT03872479.

CRISPR is a one-time treatment

Explaining the gene-editing process, Dr. Chen shared some biology basics on DNA, RNA, and proteins, and described the potential of CRISPR gene-editing to restore cellular function. 

He described DNA as the building blocks of life, serving as a blueprint, or instructions, for all the proteins in our bodies. When the body reads the DNA, it makes RNA, which then acts like a messenger taking the instructions all over the body to make proteins. Proteins are the tools our cells need to function.

Sometimes, an abnormal change in DNA’s sequence (a mutation) causes disease. These changes can be spontaneous or can be inherited from parents. This is where CRISPR-based medicines come in. Gene editing technology may be able to treat some genetic diseases by intervening at the DNA level.

To demonstrate this process, Dr. Chen, using simple colored Lego® pieces to represent DNA and RNA, explained how CRISPR gene editing medicines contain a nuclease, or a protein that edits DNA, and a guide RNA that can go in and find a specific portion of the gene and make an edit to correct the gene abnormality. 

People living with LCA10 have a disease-causing mutation in the CEP290 gene. For EDIT-101, scientists created a specific guide RNA to find the CEP290 gene in the photoreceptor cells and remove the incorrect instructions contained in the patient’s DNA.

The drug is injected one time in one eye under the retina, creating a blister-like pocket of the drug called a bleb for EDIT-101 to treat the target area that allows retina function. Dr. Chen characterized the treatment as an effective and precise process.

“The DNA is actually edited with the genetic defect corrected,” he said. “It’s a very elegant use of science for which the Nobel Prize was given, so this is a big deal.”

Jennifer Doudna, PhD, and Emmanuelle Charpentier, PhD, won the 2020 Nobel Prize in chemistry for their 2012 discovery of CRISPR.

Still a few years to market

One of our webinar viewers asked why the process can’t be used to treat all other forms of LCA.

“It’s a long road,” Dr. Chen said. “For good reasons, the regulatory path is a long one.”

The process can take 15 to 20 years, from molecular research to studying treatment effects in animals and then humans, to undergoing the rigors of earning approval by the U.S. Food and Drug Administration.

In 2017, the FDA approved LUXTURNA,® the first, and so far, only, gene therapy for a form of LCA. Gene therapy is different than gene editing. Gene therapy entails inserting a “healthy” version of the gene to offset the effect of the mutation, while gene editing revises, removes, or replaces a mutated gene at the DNA level.

This study of EDIT-101 centers on one form of LCA and it is in its initial stages, he said.

“Each of the defects, you could add it up and it’s a long, expensive and laborious exercise. It’s a commitment on our part. None of this is easy.”

He estimated that getting the CRISPR treatment to market is still a few years away.

In answer to a question about what keeps him going amid the arduous trial-and-error process that comes with clinical research, he said, some days are very frustrating, but he feels blessed to make a difference in someone’s life.

“It’s all about the patient,” Dr. Chen said. “That makes a world of difference and makes it all worthwhile.”