Researchers have developed a new form of CRISPR technology that destroys harmful cells instead of editing their genes, while leaving healthy tissue untouched.
RT’s Three Key Takeaways:
- Cell Destruction Mechanism: Unlike traditional gene editing that makes precise cuts, the Cas12a2 protein acts by shredding the deoxyribonucleic acid (DNA) of targeted cells to induce cell death.
- High Target Specificity: The technology is activated by specific ribonucleic acid (RNA) sequences found in cancer or viruses, allowing it to eliminate pathogenic cells without affecting healthy tissue.
- Potential Cancer Application: In laboratory tests, the protein reduced the growth of human lung cancer cells by 50%, matching the efficacy of some current chemotherapy drugs.
Researchers at University of Utah Health and several international institutions have developed a new form of CRISPR technology that destroys harmful cells instead of editing their genes, according to a study published in Nature. The method uses a recently discovered protein, Cas12a2, which acts by shredding the genome of a cell once it identifies a specific target.
In common CRISPR gene editing, a protein called Cas9 recognizes a specific DNA sequence and makes a single precise cut. Cas12a2 also recognizes a specific genetic sequence, but it targets an intermediate gene product called RNA rather than DNA itself. Once Cas12a2 recognizes its target, it begins cutting DNA indiscriminately until the cell self-destructs.
“Its goal is not to correct anything,” said Yang Liu, assistant professor in biochemistry at University of Utah Health and one of the study’s co-senior authors. “Instead, it’s to destroy anything it sees.”
The research team tested the technology on a KRAS gene mutation, which is known to drive cancerous growth. Cas12a2 reduced the growth of human lung cancer cells containing this mutation by 50% in a laboratory dish. Researchers noted this performance was comparable to cisplatin, a common chemotherapy drug. However, unlike traditional chemotherapy, the Cas12a2 treatment did not impact cells with healthy KRAS genes.
“The enzyme that we’re working with is extremely specific,” said Liu. “It does not touch the healthy cells. So if we’re thinking about a cancer therapy, you’re treating cancer with no side effects. That was striking to us.”
The technology also demonstrated success against human papillomavirus (HPV). Collaborators at Akribion Therapeutics found that Cas12a2 reduced the growth of HPV-infected cells by more than 90% without harming healthy cells.
“Our technology provides us with a powerful tool for sequence-specific depletion of pathogenic cells,” said Paul Scholz, co-founder and head of research and development at Akribion Therapeutics.
Injecting HPV-targeted Cas12a2 into virus-infected tumors in mice also slowed tumor growth, indicating the strategy can work in animal models. Researchers suggested the protein could be programmed to target other viral diseases, including human immunodeficiency virus (HIV).
While the results are promising, researchers cautioned that Cas12a2 has primarily been tested in laboratory dishes. Further research is required to determine the safety and efficacy of the protein in animal models before human clinical trials can begin. Challenges include ensuring the protein is delivered effectively to the necessary parts of the body and understanding how its presence affects different organ systems.
“If you try to treat an organism, different organ systems might uptake Cas12a2,” said Jared Thompson, graduate researcher in biochemistry at University of Utah Health. “And we don’t yet know how just the presence of the protein, even if it’s not being activated, affects an organism.”
Despite these hurdles, the research team suggested the technology could eventually be applied to various healthcare fields, including the treatment of neurodegenerative diseases or aging-related conditions.
“Because Cas12a2 can be programmed with a guide RNA to target any RNA sequence, and it shows little to no off-targeting, we believe we have discovered a way to selectively kill cells across all of biology,” said Ryan Jackson, associate professor of chemistry and biochemistry at Utah State University. “We envision this technology will transform science, agriculture, and medicine in ways previously unavailable.”
