Cells Are the New Cure by Robin L. Smith MD

Author:Robin L. Smith, MD [Max Gomez, Robin L. Smith]
Language: eng
Format: epub
ISBN: 9781944648848
Publisher: BenBella Books, Inc.

CRISPR IN HUMAN TRIALS

Feng Zhang, PhD, whom we noted in chapter nine as one of the bioengineers essential to the invention of CRISPR, expects to begin human trials in 2017 using CRISPR to treat a rare eye disease called Leber congenital amaurosis (LCA), also discussed in chapter nine in the case of the child Clara. Affecting about one in every 80,000 infants, the condition is usually diagnosed early in life and quickly leads to complete blindness.

This is a nearly ideal condition on which to test CRISPR inside a patient’s body for several reasons. The eye is an attractive test site because cells engineered by CRISPR can’t travel from the compartment of the eye to other areas of the body; any potential danger starts and stops inside an eye that is or soon will be blind anyway. Moreover, the subset of LCA that will be the subject of this trial is caused by a single malfunctioning gene; fix this one gene, and you’ve fixed the problem. Also, the eye is easy to reach with treatments. And finally, LCA has already been the test disease for the first experimental gene therapies using strategies other than CRISPR. In 2008 doctors used a viral delivery system to splice healthy copies of the gene RPE65 into the DNA of eye cells in people suffering from a variety of LCA related to that gene. The journals Human Gene Therapy and Molecular Therapy both reported that a year and a half later many patients in the trial regained sight and that there had been very few side effects. With successful gene therapy already directed at LCA, it’s not a giant leap to accomplish the same genetic insertion via a new technology.

In fact, the trial conducted by Zhang’s Cambridge, Massachusetts, company Editas will use viruses as well, but instead of using them directly to insert a healthy gene into malfunctioning eye cells, these viruses will manufacture the components of a CRISPR system. Once assembled inside the eye, the CRISPR-Cas9 system will delete about 1,000 DNA letters from the CEP290 gene in the patient’s photoreceptor cells and replace these with 1,000 new letters. Laboratory experiments leading up to the approval of the trial showed that the gene should function correctly again after the CRISPR edit.

Even sooner, the University of Pennsylvania will oversee a trial that uses CRISPR outside the body to engineer a patient’s T cells to attack cancer. This trial (which is not against a rare disease, but has implications for the field) puts a CRISPR spin on the CAR-T T-cell therapy profiled in chapter five and on cancer immunotherapy. In this technique, T cells harvested from a patient’s blood are engineered to recognize specific proteins that mark the surfaces of cancer cells and are then reinfused into the patient’s body to find and fight the disease. In the Penn trial, CRISPR will be the mechanism of this ex vivo (outside the body) engineering.

Specifically, led by immunotherapy pioneer Carl June, MD, the group will use tried-and-true techniques (targeting

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