First CRISPR trial on humans set to begin

HIV - Researchers   successfully modified the T cells of 12 HIV patients to resist infection. - Photo Penn Medicine

Researchers from the Perelman School of Medicine successfully used a genome-editing technology to modify the T cells of 12 HIV patients to resist infection. – Photo: Penn Medicine

On June 21, the National Institutes of Health gave permission for starting the first ever clinical trial using CRISPR genome-editing technology, Nature news notes. The trial, which  will begin before the end of the year, will be carried out on 18 cancer patients to “help augment cancer therapies that rely on enlisting a patient’s T cells, a type of immune cell”.

The goal of the trial is not to cure cancer but to test the safety of CRISPR-Cas9 technology. According to Nature, the T cells from the patients suffering from melanoma, sarcoma or myeloma will be removed and three edits will be performed using CRISPR.

The first one will be to insert a gene for a protein engineered to detect cancer cells and instruct the T cells to target them, the second edit will be clean up the T cells so they don’t interfere with the process and finally the third edit will be to “remove the gene for a protein that identifies the T cells as immune cells and prevent the cancer cells from disabling them”. The cells will be returned to the patients once all the three edits are completed.

CRISPR is not the only genome-editing technology around.  However, CRISPR is far better than other technologies as editing is far easier and more efficient. But it does have some inherent problems.  According to the journal, CRISPR has a propensity for going in off-target edits. “These are instances in which the system cuts or mutates unintended parts of the genome. And despite precautions, the immune system could still attack the edited cells,” it says.

Though this is the first time that permission has been granted for a human clinical trial involving CRISPR, another genome-editing technology was used in the past.  The enzymes called zinc-finger nucleases (ZFNs) were used to genetically engineer the immune cells of 12 people with HIV, to resist infection, and decrease the viral load of some patients taken off antiretroviral therapy. The results published in The New England Journal of Medicine on March 5, 2014 was the first time gene editing approach was used in a trial on humans.

After four weeks of infusing the edited immune cells back into the patients, six subjects were taken off HIV medications for 12 weeks. While two were put back on treatment, the viral load decreased on average by 10 fold at the end of the 12-weeks treatment interruption.

Also, one week after the initial infusion, the decrease in the modified T cells was significantly less than the unmodified T cells during the period of treatment interruption. “The modified cells were also observed in the gut-associated lymphoid tissue, which is a major reservoir of immune cells and a critical reservoir of HIV infection, suggesting that the modified cells are functioning and trafficking normally in the body,” a release notes.

“This study shows that we can safely and effectively engineer an HIV patient’s own T cells to mimic a naturally occurring resistance to the virus, infuse those engineered cells, have them persist in the body, and potentially keep viral loads at bay without the use of drugs,” corresponding author Carl H. June from Perelman School of Medicine, University of Pennsylvania said in the release.


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