First-Of-Its-Kind CRISPR Editing in Living Person Performed

Scientists at Oregon Health and Science University (OHSU) in Portland, Oregon have performed the first-ever CRISPR gene editing procedure for a living person.  This procedure was undertaken to address a blindness-causing gene mutation, and the goal is to restore vision to a patient with congenital blindness.

CRISPR refers to the technology that performs precise genomic editing of cells. Often times used in biological research in cells or animals to experiment with removing or adding a gene, this procedure marks the first time CRISPR has been used to edit human genes within the body, a process also referred to as in vivo gene editing. This experiment is intended to be the first in a clinical trial called BRILLIANCE, which aims to enable sight in people born with a blindness-causing mutation. The BRILLIANCE clinical trial is sponsored by Allergan and Editas Medicine.

Gene-editing methods previous to this trial have involved editing genetic material after it was removed from the body. The trial’s gene editing approach is designed to be permanent, but the genetic changes are not expected to be passed onto the offspring of the individuals who have had experienced the procedure.

Clinicians with OHSU’s Casey Eye Institute performed the procedure for the BRILLIANCE clinical trial, and the intention is to repair mutations in the CEP290 gene.  These mutations are known to cause a rare form of inherited blindness called Leber congenital amaurosis type 10; also known as LCA10 and CEP290-related retinal dystrophy. Most people who inherit this mutation are either born blind or become blind within the first decade of their life.

The BRILLIANCE Phase I/II clinical trial is intended to study the safety, tolerability, and efficacy of CRISPR technology in about 18 patients with LCA10. Researchers expect to have up to five cohorts of patients across three dose levels. Both pediatric patients age three to 17 years, and adults, are eligible for the trial. The patients will be given a single dose of AGN-151587 by way of a subretinal injection in one eye.

This injection will be of microscopic droplets that carry a hollowed-out virus engineered to deliver the genetic instructions to manufacture the CRISPR gene-edits. This is a variation of gene therapy, where a preferable gene is delivered via a harmless virus.

“Being able to edit genes inside the human body is incredibly profound,” said Mark Pennesi, M.D., Ph.D., who leads OHSU’s involvement in the trial and is the Kenneth C. Swan associate professor of ophthalmology in the OHSU School of Medicine; and, chief of the OHSU Casey Eye Institute’s Paul H. Casey Ophthalmic Genetics Division. “Beyond potentially offering treatment for a previously untreatable form of blindness, in vivo gene editing could also enable treatments for a much wider range of diseases.”

“The first patient dosed in the BRILLIANCE clinical trial marks a significant milestone toward delivering on the promise and potential of CRISPR medicines to durably treat devastating diseases such as LCA10. We look forward to sharing future updates form this clinical trial and our ocular program,” said Cynthia Collins, president and chief executive officer of Editas.

Academic institutions currently involved in the trial include: OHSU; Bascom Palmer Eye Institute in Miami, Florida; Massachusetts Eye and Ear in Boston, Massachusetts; and W.K. Kellogg Eye Center at the University of Michigan in Ann Arbor, Michigan.

OHSU’s Casey Eye Institute currently is involved in 14 different clinical trials investigating new genetic treatments for ophthalmic conditions and about 50 vision-related clinical trials overall.

The results from this procedure will not be known for some time, but based on the previous success CRISPR has demonstrated in genetic editing in animal models, it is very likely to be successful.

Although CRISPR has been used in the laboratory and in a small number of patients with cancer, sickle cell anemia or beta-thalassemia, in those cases, cells were removed the bodies of patients, edited using CRISPR, then infused back into the patients.

The results from this first-of-its-kind trial will be astronomical in the clinical space far beyond this particular genetic mutation, and will be impactful for patients and medical professionals who work in any field impacted by genetic diseases. CRISPR holds the potential to change the genetically coded information an individual was born with, and the ability to modify any gene, an ability that incurs a great deal of ethical implications and oversight.

The ability to “fix” any mutation would mean genetic mutations would hold little permanence, and can be reversed upon discovery.

In recent years, scientists in China have come under scrutiny for using CRISPR to produced genetically engineered human babies for lack of ethical oversight. The procedure performed at OHSU opens the door for more medically sanctioned genetic experimentation in those who suffer from congenital mutations.