Scientists at Utah State University have created an enzyme that can destroy the genes of cancer cells, causing them to self-destruct.
The enzyme, called Cas12a2, can be programmed to recognize a specific RNA, such as the type produced by cancer cells. Once it finds the target RNA, the enzyme cuts the cell’s genome into fragments. The new research, published in two papers in Nature, could be developed into a solution for destroying cancer cells that are difficult to target with conventional drugs.
Initially, the research team approached Cas12a2 as a gene-editing tool for use in CRISPR. A series of experiments failed because Cas12a2 became uncontrollable and indiscriminately cut DNA after recognizing RNA that matched the guide RNA, whereas the goal of the Cas enzyme is to cut at the correct location to edit or insert genetic information. They found this to be a natural mechanism that helps limit the spread of infection within a population and exploited it to kill cancer cells in two different ways.
One way is to direct Cas12a2 to RNA produced by cells, specifically cells carrying mutations in the TP53 gene. This gene is mutated in about half of all cancer cases. According to Genecards, TP53 is located on chromosome 17 and is responsible for controlling the cell cycle and killing abnormal cells. The second way is to have an enzyme target RNA caused by a mutated KRAS gene – which can cause cells to grow uncontrollably and become cancerous.
An enzyme capable of cutting DNA has been exploited to kill cancer cells. Image: Science Photo Library
In both cases, Cas12a2 showed high specificity, killing cells carrying the cancer-related gene mutation, even when that mutation differs from normal RNA by only a single character. Tests have shown effectiveness on human cells cultured in the laboratory. In live mice, the enzyme shrinks tumors.
This technology shows greater selectivity than current chemotherapy, which destroys all rapidly dividing cells in the body, according to Jingkun Zeng, a cancer biologist at the Gladstone Institute in the US.
According to Baojun Wang, a synthetic biologist at Zhejiang University in China, there is still a long way to go from experiments to a therapy that can be tested on humans. The current hurdle is how to get Cas12a2 into cells, as it is a large molecule. The enzyme has also not yet destroyed all cancer cells in experiments, and more safety tests are needed to ensure Cas12a2 does not harm healthy cells.
However, Wang considers the studies to be landmark evidence of a promising technology. The scope of application could extend to autoimmune and neurological diseases, provided the disease is associated with a specific type of RNA.
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