IR-A ASO targets the exon 10-12 junction in of IR-A mRNA.
Invention Summary:
Breast cancer is one of the most common cancers among women, and while effective treatment options exist, there remains a critical need to enhance their efficacy and reduce their off-target effects to minimize toxicity. Expression of Insulin receptor-A (IR-A), one of two isoforms of the insulin receptor, is correlated with worsened breast cancer prognosis and resistance to therapy. Previous attempts to knock-down transcripts encoding IR-A resulted in nonselective knockdown of both IR isoforms, due to its high similarity with IR-B, the second IR isoform. Since IR-B is the primary regulator for glucose homeostasis, developing a tool that specifically targets IR-A is essential. There is currently no alternative other than genetic modification for selectively reducing IR-A.
Rutgers researchers developed novel antisense oligonucleotides (ASOs) to specifically target IR-A mRNA. The IR-A ASO selectively targets the exon 10-12 splice junction site present in IR-A, and does not target IR-B. The specificity and efficacy of the ASO was tested in breast cancer, prostate cancer and sarcoma cell lines. IR-A knockdown, upon IR-A administration, was successful in all three cancer cell lines with minimal off-target knockdown of IR-B. The efficacy of the IR-A ASO enhances the potential for studying IR-A function in the context of cancer.
Market Applications:
Onco-therapeutic for breast, prostate, and other cancers overexpressing IR-A
IR-A ASO research tool
Advantages:
Targeted therapy
Potential treatment with reduced toxicity
Inhibition of IR-A oncogenic function
Publications:
• Galifi CA, Dikdan RJ, Kantak D, Bulatowicz JJ, Maingrette K, Gunderson SI, et al. Identifying antisense oligonucleotides for targeted inhibition of insulin receptor isoform A. Front Oncol. 2025;15:1563985.
Intellectual Property & Development Status: PCT patent application filed and pending. Available for licensing and/or research collaboration. For any business development and other collaborative partnerships contact marketingbd@research.rutgers.edu