Researchers in Australia are shining a spotlight on a safer delivery method for targeted CRISPR gene therapies—and they’re using literal illumination to pull it off.
Scientists and biomedical engineers from the University of New South Wales Sydney say they've developed a light-sensitive liposome that can ferry CRISPR molecules to specific sites in the body. When hit with LED light, the liposomes unleash their CRISPR payloads to hunt down faulty genes.
The CRISPR-Cas9 gene-editing tool consists of a guide RNA that homes in on a target in the DNA, and the Cas9 enzyme, which cuts the DNA much like a pair of molecular scissors. A slate of companies is exploring the technology to treat cancer and even blindness, but the therapy is traditionally delivered using viruses, which can themselves spur unwanted immune responses and other side effects.
Liposomes, on the other hand—well established in the drug delivery field—boast a proven safety track record, plus, they’re quite easy to make, Wei Deng, Ph.D., lead research author, said in a release.
“These ‘bubbles’ are relatively simple to prepare, can be filled with appropriate medication and then injected into the body," she said.
Using LED light, the team can activate the liposomes up to a centimeter below the skin, Deng said. To go any deeper—to target a tumor, for instance—the team thinks it could scramble the photophobic liposomes using X-ray, something it’s already proven is possible in earlier research.
The researchers have so far trialed their system in cell lines and animals and recently published their findings in the journal ACS Applied Materials and Interfaces. The liposomes won out in in vitro testing, successfully knocking out the eGFP gene in human HEK293/GFP cells and the TNFAIP3 gene in TNFα-induced HEK293 cells, and further hit a 77% knockout rate in zebrafish.
It will take some time before the researchers can study their delivery system in humans, but they’re already plotting future animal trials evaluating X-ray to deliver CRISPR gene-splicing molecules for deep cancer treatment.
“By using X-ray instead of light we also need to find a proper animal model that might translate to using this technology for something like breast cancer treatment,” Deng said. “So we’re looking for collaborators who have this sort of expertise.”