Although small RNA molecules can regulate gene expression with precision, which makes them potentially new cancer therapies to slow down the growth of cancer cells, effectively delivering small RNAs to solid tumors continues to be a challenge for scientists. However, researchers at the Koch Institute for Integrative Cancer Research at MIT have recently reported, in the journal Proceedings of the National Academy of Sciences, that a lipid/polymer nano particle successfully delivered small RNAs in a lung cancer mouse model, both delaying and shrinking tumor growth.
According to the study, entitled “Small RNA combination therapy for lung cancer,” this new lung-targeting nanoparticle is capable of delivering a microRNA mimic, called miR-34a, combined with a small interfering RNA (siRNA), into lung adenocarcinoma cells in vitro and into tumors. The delivery of the microRNA is based on activation of oncogenic Kirsten rat sarcoma viral oncogene homolog (Kras) and loss of p53 function.
Researchers report that the delivery of miR-34a restored its levels in lung tumors, down-regulating its target genes and slowing tumor growth. Delivering siRNAs targeting Kras, on the other hand, reduced Kras gene expression and MAPK signaling, increased apoptosis (the process of programmed cell death), and inhibited tumor growth.
Furthermore, the combination of these two molecules improved therapeutic responses, compared to those who had either of these small RNAs alone. As a result, the combination led to tumor regression.
Dr. Tyler Jacks, Director at the Koch Institute, noted in a recent MIT press release,“Small-RNA therapy holds great promise for cancer. It is widely appreciated that the major hurdle in this field is efficient delivery to solid tumors outside of the liver, and this work goes a long way in showing that this is achievable.”
Indeed, the data that researchers compiled from the study reveal positive potential of developing efficient RNA delivery that could be used in the future as a therapeutic strategy that can customized to a specific patient’s needs and that would be able to effectively regulate cancer cells’ genetic mutations. In addition, RNA therapies based on this new research could be combined along with traditional cancer therapies, such as chemotherapy, for enhanced results.
James Dahlman, a graduate student and co-first author of the study, concluded in the press release that, “RNA therapies are very flexible and have a lot of potential, because you can design them to treat any type of disease by modifying gene expression very specifically. We took the best mouse model for lung cancer we could find, we found the best nanoparticle we could use, and for one of the first times, we demonstrate targeted RNA combination therapy in a clinically relevant model of lung cancer”
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