Scientists at The Scripps Research Institute (TSRI) developed a compound to target a specific microRNA — miR-96 — that was seen to selectively decrease the growth of triple-negative breast cancer in mice. The findings were published in the journal Proceedings of the National Academy of Sciences, in the study “Design of a small molecule against an oncogenic noncoding RNA“.
MicroRNAs are small non-coding RNAs that inhibit protein production from specific genes by binding to their intermediate RNA molecules and inducing their degradation. A number of microRNAs have been associated with a variety of diseases, including cancer. The target of this study, miR-96, has been shown to promote cancer progression by decreasing cancer cell death.
Researchers used a computational approach, named Informa, to design and develop small molecules that target loops in the RNA, which are very common in microRNA precursors. A precise combination of these molecules generated a compound, which the authors named Targaprimir-96, that specifically targeted the microRNA-96 in breast cancer cells, leading to programmed cell death.
“This is the first example of taking a genetic sequence and designing a drug candidate that works effectively in an animal model against triple negative breast cancer,” Matthew Disney, the study’s senior author and a professor of chemistry at TSRI, said in a press release. “The study represents a clear breakthrough in precision medicine, as this molecule only kills the cancer cells that express the cancer-causing gene — not healthy cells. These studies may transform the way the lead drugs are identified — by using the genetic makeup of a disease.”
The team tested the compound in mice models of triple-negative breast cancer, treating them with targaprimir-96 for 21 days. Results revealed that the compound was able to decrease miR-96 production in vivo and, more importantly, that such decrease resulted in reduced tumor growth due to an increase in cancer cell death.
Another important finding was that, contrary to typical cancer treatments that target malignant and healthy cells indiscriminately and often have severe side effects, targaprimir-96 was highly selective for cancer cells, leaving healthy cells unaffected.
These findings suggest that this approach may be used to develop new drugs that more selectively target molecules involved in the biology of diseases, instead of the commonly used expensive and time-consuming, high-throughput screens that test millions of potential drug candidates.
“In the future we hope to apply this strategy to target other disease-causing RNAs, which range from incurable cancers to important viral pathogens such as Zika and Ebola,” said Sai Pradeep Velagapudi, a research associate and the study’s first author.