• Technical Name
  • Operator
  • National Cheng Kung University
  • Booth
  • Online display only
  • Contact
  • 陳若瑜
  • Email
  • forman7770@hotmail.com
Technical Description This technology is the novel double-stranded short interfering ribonucleic acid (siRNA) capable of directing the cleavage of over-expressed Aurora-A gene mRNA in cancers. Also this technology is use of the novel siRNA for manufacturing a medicament suitable for treating cancers, which is mediated through epidermal growth factor receptor (EGFR) signaling. Accordingly, a pharmaceutical composition comprising the disclosed novel siRNA molecules is provided, one strand of siRNA molecule comprises at least contains one locked nucleic acid (LNA) molecules; as well as a method of treating a subject suffering from EGFR-mediated cancer via administering to the subject.
Scientific Breakthrough Abnormal expression of Aurora-A and EGFR have been observed in various types of cancer cells; and EGF is known to specifically increase the translation of Aurora-A mRNA possibly via forming a translation pre-initiation complex on the 5’-UTR region of Aurora-A mRNA; hence, Aurora-A mRNA 5’-UTR has been hypothesized to be a potential target for developing therapy to EGFR-associated cancers. In the past 20 years, small molecule inhibitors have been used to inhibit the kinase activity of overexpressed Aurora-A in cancers; however, those inhibitors lack specificity and may cause serious side effects. The specific LNA-modified siRNAs can selectively target the specific exon of Aurora-A mRNA 5-UTR to inhibit its translation.
Industrial Applicability The selective Aurora kinas A siRNA – siRNA-2 is a specific and safe siRNA that can inhibit the expression of Aurora-A in cancer cells. In addition, the LNA-modified siRNA-2 is more stable and has a better efficacy in inhibiting the Aurora kinas A. LNA-siRNA-2 can selectively kill cancer cells through targeting Aurora kinase A without any effect on normal cells. The IC50 of the modified siRNA-2 is around 5 nM and 11 nM for colorectal cancer cells and hepatocellular carcinoma, respectively. By xenograft animal model, the LNA-siRNA-2 can effectively inhibit the tumor growth. In summary, LNA-siRNA-2 has an excellent anti-cancer effect and patent protection.
This novel siRNA-2 for cancer therapy is a valuable potential drug for further development.