| 2023-KASI-70078 | |
| Purdue researchers have developed a chemically modified microRNA (miRNA) that is an anticancer agent. Unmodified RNAs are subject to serum and intracellular nucleases leading to rapid degradation and a short half-life. This chemical instability has resulted in miRNA therapeutics often requiring high and repetitive dosing to achieve a therapeutic response. Purdue researchers have a developed a fully modified miRNA, which has an over 400-fold increase in stability relative to its unmodified version and without compromising activity. This approach is particularly promising towards developing anticancer agents because certain miRNAs, such as miR-34a, are frequently overexpressed in cancer. Further, pertaining to miR-34a, downregulation of targets of miR- 34a have been shown to lead to inhibition of several types of cancers. With the aim of developing anticancer agents, researchers have been able to fully chemically modify miR-34a with 2′-O-methyl, 2′-fluoro ribose bases, and phosphorothioate linkages to create conjugates of miR-34a. Administration of these conjugates, which are composed of fully modified miR-34a (FM-miR-34a) conjugated to folate, results in specific delivery to tumor tissue leading to a strong inhibition of tumor proliferation and delayed tumor growth. The FM-miR-34a robustly inhibits the activity of miR-34a targets, affecting repressing a greater number of them, as compared to partially modified miR-34a. Many of these developed conjugates have demonstrated notable inhibition of miRNA interactions within cells, as shown by their ability to disrupt pathways critical to the survival and proliferation of lung, breast, ovarian, and prostate cancer cells. Technology Validation: - MB-231 cells were transfected with PM-miR-34a or FM-miR-34a for measurement of tumor inhibition - Significant decrease in tumor volume was seen for tumors harvested from mice implanted with transfected breast cancer cells - Western blot analysis following a single 1.5 nmol intravenous injection of folate-FM-miR-34a highlights decreases expression of miR-34a targets (MET, CD44 and AXL) in comparison to folate-PM-miR-34a and Fol-NC - Intravenous injection of four 1 nmol doses of folate-FM-miR-34a at six day intervals reduced preformed MB-231 breast cancer xenografts, leading to complete cures in some mice. Advantages: - Allows for the specific targeting of miRNA-cancer cell interactions, resulting in a more personalized and precise approach to cancer treatment - Treatment can be tailored to specific types of cancers, leading to more effective treatments - Full modification of miRNA enhances stability, increasing resistance to serum nucleases and boosting the intracellular half-life, making the treatment more durable and longer lasting Applications: - Treatment of various types of cancers |
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Mar 23, 2023
Provisional-Gov. Funding
United States
(None)
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Purdue Office of Technology Commercialization The Convergence Center 101 Foundry Drive, Suite 2500 West Lafayette, IN 47906 Phone: (765) 588-3475 Fax: (765) 463-3486 Email: otcip@prf.org |
