Researchers have identified a new type of CRISPR technology that functions more like a paper shredder than traditional gene editing tools. Unlike the well-known Cas9 protein which makes precise DNA edits, the recently discovered Cas12a2 protein can be programmed to destroy the genomes of specific target cells, offering potential new methods for treating cancer and viral infections.
The technology works by recognizing a specific genetic sequence within an intermediate RNA product. Once Cas12a2 identifies its target, it begins cutting DNA continuously until the cell is overwhelmed by damage and undergoes self-destruction.
Yang Liu, PhD, an assistant professor in biochemistry at U of U Health and co-senior author of the study, stated that the goal of the protein is to destroy anything it sees rather than correcting genetic information. Because the system can be programmed to activate only when encountering specific RNA sequences, researchers can direct it to target cells containing cancer mutations or viral signatures.
In laboratory tests involving human lung cancer cells with a KRAS mutation, Cas12a2 reduced cell growth by 50%, performing similarly to established drugs like cisplatin. Notably, the enzyme did not affect healthy cells with normal KRAS. Liu noted that the high level of specificity was striking because it suggests a way to treat cancer without causing side effects.
The protein has also shown effectiveness against infectious diseases. When researchers targeted Cas12a2 to viral RNA from the human papillomavirus (HPV), collaborators at Akribion Therapeutics found that it reduced the growth of infected cells in a dish by more than 90% without harming healthy cells.
Testing in mouse models also showed that injecting HPV-targeted Cas12a2 into virus-infected tumors slowed tumor growth. Researchers suggested that this technology could potentially be programmed to target other viral diseases, such as HIV.
Despite the promising results in cells and animal models, significant challenges remain before human therapies are possible. Researchers noted that more work is required to ensure safety and efficacy in humans, specifically regarding how the presence of the protein affects different organ systems and how to effectively deliver enough of the protein to targeted body parts.
Ryan Jackson, PhD, an associate professor at Utah State University and co-senior author, expressed optimism that the technology could transform medicine, agriculture, and science due to its ability to selectively kill cells across biology.
