CRISPR Safety Under the Microscope

CRISPR gene editing (see Pulse 22) is rightly hailed as a potential game-changer in future medicine, but recent news released by Karolinska Institutet and Novartis Institutes for Biomedical Research underline that current CRISPR therapies could increase the risk of cancer (see below).

In fact, editing cells’ genomes with CRISPR-Cas9 might increase the risk that the altered cells, intended to treat disease, will trigger cancer, two studies published on Monday warn, as reported by Scientific American. This could be bad news for the companies developing CRISPR-based therapies. However, an article published in Seeking Alpha, a resource for investors, suggests to hold and even invest more in CRISPR-related stocks.

“CRISPR-Cas9 is a powerful tool with staggering therapeutic potential,” said Dr Bernhard Schmierer, research leader at Karolinska Institutet. “Like all medical treatments however, CRISPR-Cas9-based therapies might have side effects, which the patients and caregivers should be aware of. Our study suggests that future work on the mechanisms that trigger p53 in response to CRISPR-Cas9 will be critical in improving the safety of CRISPR-Cas9-based therapies.”

This approach seems the best one: Further research in CRISPR will, besides developing new therapies, also address the safety aspects of gene editing.

CRISPR gene editing could increase cancer risk. Researchers at Karolinska Institutet have suggested that therapeutic use of CRISPR-Cas9 gene editing may increase the risk of cancer, according to a new study. A research paper published in Nature Medicine indicates that the use of CRISPR-Cas9 in human cells in a laboratory setting can activate a protein known as p53, which is known to contribute to making cells grow uncontrollably and become cancerous. Another study by the Novartis Institutes for Biomedical Research, also published in Nature Medicine, reports similar results. According to the scientists, more studies are required in order to guarantee the safety of these CRISPR-Cas9 “molecular scissors” for gene-editing therapies.

Camouflaged nanoparticles deliver killer protein to cancer. Scientists at Penn State have shown that a biomimetic nanosystem can deliver therapeutic proteins to selectively target cancerous tumors. Using a protein toxin called gelonin from a plant found in the Himalayan mountains, the researchers caged the proteins in self-assembled metal-organic framework (MOF) nanoparticles to protect them from the body’s immune system. The researchers studied the effectiveness of the nanosystem and its toxicity in a small animal model and reported their findings in a cover article in the Journal of the American Chemical Society.

Spider silk microcapsules deliver vaccine to immune cells. Researchers from the universities of Geneva, Freiburg, Munich, and Bayreuth, in collaboration with the German company AMSilk, have developed spider silk microcapsules capable of delivering vaccine directly to the heart of immune cells. A research paper published in Biomaterials indicates that this process can strengthen the efficacy of vaccines on the immune system -- and in particular on T lymphocytes, specialized in the detection of cancer cells. According to the scientists, the process could also be applied to preventive vaccines to protect against infectious diseases, and constitutes an important step towards vaccines that are stable, easy to use, and resistant to the most extreme storage conditions.

Regenerative cell opens new frontier for medicine. Researchers at the Stowers Institute for Medical Research have isolated a cell that is capable of regenerating an entire organism. With a new technique that combines genomics, single-cell analysis, flow cytometry and imaging, scientists have isolated this amazing regenerative cell, which enables creatures such as the planarian flatworm to regrow missing limbs and even a severed head. The research results, published in Cell, will likely propel biological studies on highly regenerative organisms like planarians and also inform regenerative medicine efforts for other organisms like humans that have less regenerative capacity.

Hydrogel helps breathing after spinal cord injury. Scientists at Thomas Jefferson University have demonstrated that a hydrogel could help repair damaged spinal nerves that control breathing, an advance that could eventually be developed into new patient treatment. A study published in Journal of Neuroscience describes the design and laboratory tests of a hydrogel that releases a nerve-protecting agent at the site of injury, restoring independent breathing in rat models. The researchers are now exploring the ideal timing and dosing for applying the biogel, to assess whether it could work in instances where treatment isn’t immediately available after injury.

Device attaches to damaged heart, enabling delivery of therapy. Scientists at MIT and other labs have developed a device that can deliver medicine from a port under a patient’s skin to augment cardiac function. The device, called “Therepi,” contains a reservoir that attaches directly to the damaged heart tissue. A refill line connects the reservoir to a port on or under the patient’s skin where therapies can be injected by either healthcare professionals or by the patients themselves. A study with laboratory mice, published in Nature Biomedical Engineering, shows that Therepi is effective for improving cardiac function after a heart attack.