NEW GENE EDITING CRISPR
The first human test in the U.S. involving the gene-editing tool CRISPR could begin at any time and will employ the DNA cutting technique in a bid to battle deadly cancers.
Doctors at the University of Pennsylvania say they will use CRISPR to modify human immune cells so that they become expert cancer killers, according to plans posted this week to a directory of ongoing clinical trials.
The study will enroll up to 18 patients fighting three different types of cancer—multiple myeloma, sarcoma, and melanoma—in what could become the first medical use of CRISPR outside China, where similar studies have been under way.
An advisory group to the National Institutes of Health initially gave a green light to the Penn researchers in June 2016, but until now it was not known whether the trial would proceed.
"We are in the final steps of preparing for the trial, but cannot provide a specific projected start date,” a spokesperson for Penn Medicine told MIT Technology Review.
The Parker Institute for Cancer Immunotherapy, a charity set up by billionaire entrepreneur Sean Parker, one of the founders of the music-sharing site Napster, confirmed it is helping to finance the study.
The CRISPR trial, led by doctor Edward Stadtmauer, involves reprogramming a person’s immune cells to find and attack tumors.
To help enhance the treatment, Penn scientists intend to use CRISPR to delete two genes in patients’ T cells to make them better cancer fighters. One of the genes to be removed makes a “checkpoint” molecule, PD-1, that cancer cells exploit to put brakes on the immune system.
A further edit will delete the receptor that immune cells normally use to sense danger, like germs or sick tissue. An engineered receptor, added in its place, will instead steer them toward particular tumors.
In the study, doctors will remove people’s blood cells, modify them with CRISPR in the lab, and then infuse them back into the patients.
This outside-the-body approach, called ex vivo gene therapy, is considered less risky than injecting CRISPR directly into a person’s bloodstream, which could cause immune reactions.
A second CRISPR trial that could begin in Europe later this year will also pursue the ex vivo approach. CRISPR Therapeutics, a biotech company based in Cambridge, Massachusetts, asked European regulatory authorities in December for permission to try to cure beta thalassemia, a blood disorder, by making a genetic tweak to people’s blood cells.
Scientists use ‘molecular-Lego’ to take CRISPR gene-editing tool to the next level
FORNASARI PIER MARIA
DECEMBER 13, 2016
A team of researchers at Western University is playing with molecular-Lego by adding an engineered enzyme to the revolutionary new gene-editing tool, CRISPR/Cas9. Their study, published today in the Proceedings of the National Academy of Sciences (PNAS), shows that their addition makes gene-editing more efficient and potentially more specific in targeting genes.
The scientific community is buzzing with the promise that CRISPR offers for human gene-editing, opening the door to use gene-therapy to treat diseases like cystic fibrosis and leukemia.
In cystic fibrosis, for example, there is one gene mutation which causes the disease in a very large proportion of patients. If it were possible to use CRISPR to cut that mutation out of the genome, the disease could potentially be cured.
“The problem with CRISPR is that it will cut DNA, but then DNA-repair will take that cut and stick it back together,” said the study’s principal investigator, David Edgell, associate professor at Western’s Schulich School of Medicine & Dentistry. “That means it is regenerating the site that the CRISPR is trying to target, creating a futile cycle. The novelty of our addition, is that it stops that regeneration from happening.”
scissors-facebook-imageThe Western researchers have demonstrated that the creation of a new enzyme called TevCas9, which cuts the DNA in two places instead of one, makes it much more difficult for the DNA-repair to regenerate the site of the cut. The researchers created TevCas9 by adding an enzyme called I-Tevl onto the nuclease, Cas9, which is the typical enzyme used to cut DNA in CRISPR.
The study also showed that the addition of Tev shows promise at being much more specific in targeting genes and less likely to cause off-target effects in the genome, which is a significant problem for any potential therapeutic application.
“Because there are two cut-sites, there is less chance that these two sites occur randomly in the genome; much less chance than with just one site,” said co-author Caroline Schild-Poulter, associate professor at Schulich Medicine & Dentistry and a scientist at Robarts Research Institute. “This remains to be tested, but this is the hope and the expectation.”