RARE Daily

Researchers Show Safer Way to Deliver CRISPR Gene Therapy

November 13, 2020

Rare Daily Staff

Light-activated liposomes could help to deliver CRISPR gene therapy, a method that could prove safer and more direct than those currently in use, according to researchers at the University of New South Wales in Sydney, Australia.

A multi-institutional UNSW team involving biomedical engineers and scientists has found that liposomes—commonly used in pharmacology to encapsulate drugs or genes—can be triggered by light to release the payload in a specific site of the body.

The team, which reported the findings in ACS Applied Materials and Interfaces, demonstrated their results in cell lines and animal models, with more research needed to test and confirm their method in humans.

Until now, CRISPR gene therapy technology, which uses a guide RNA to seek out faulty gene sequences and a Cas9 protein to cut or replace it with healthy versions, has used viruses loaded with the CRISPR molecules that then move through the body to find the targeted cells.

While the technology has proved revolutionary, with researchers who developed it having received the Nobel Chemistry prize this year, the use of viruses as the delivery vehicle is less than ideal because of the potential for adverse immune response and toxicity.

In the latest research, the team demonstrated how they could use a much more benign vehicle to carry the CRISPR molecules while using a unique way to deliver them solely to the area of the body in need of them.

The team used liposomes—spherical nanostructures of fat molecules very similar to cell membrane material—to carry the CRISPR molecules to the target site in the body. Liposomes are well-established delivery vehicles for drugs and are much safer than using vaccines, says Wei Deng, lead author of the study.

“Liposomes are already well established as an extremely effective drug-delivery system,” said Deng. “These ‘bubbles’ are relatively simple to prepare, can be filled with appropriate medication and then injected into the body.”

“The traditional delivery vehicle of CRISPR is based on viruses, but they create their own problems because it is difficult to predict the reaction of patients to the viruses,” she added.

The team also discovered that light could ensure the CRISPR molecules found the right target at the right time. “When light is shone onto the liposomes, they can be disrupted at once, immediately releasing the entire payload,” said Deng.

The team found in both cell lines and animal models that when the liposomes are triggered by an LED light, they eject the CRISPR contents which go to work looking for genes of interest. In their study the light could activate the liposomes up to a centimeter below the surface of the skin.

In future studies, the team will test using X-rays to trigger CRISPR delivery in deep tissues at depths greater than one centimeter, especially for deep cancer treatment, said Deng.

“CRISPR technology has created a very promising tool for developing new targeted, gene and cell-based therapies. Its outcomes would largely increase with the desired delivery system, and in this context, our findings may provide such a system,” Deng said.

“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. So we’re looking for collaborators who have this sort of expertise.”

Photo: Study lead author Deng Wei

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