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BARD1 Life Sciences Limited (ASX:BD1), a medical technology company developing non-invasive cancer diagnostics, today announced that it has received Issue Notification from the United States Patent and Trademark Office (USPTO) confirming the issue of United States Patent no 10,273,475on 30th April 2019. US Patent no 10,273,475 entitled “Regulation of BARD1 expression by long non-coding RNA” names Irmgard Irminger-Finger and Maxim Pilyugin as inventors and has been assigned to BARD1Life Sciences Limited. The issued US patent claims are directed to siRNA that target and reduce the expression of the novel long non-coding BARD1 RNA molecule BARD1 9′L. BARD1 9’L is a therapeutic target due to its overexpression in cancer and siRNA could be potentially used for treatment of cancer. The patent application was filed on 12July2015and is due to expire on 12 July 2035. A US continuation application has been filed to further protect methods to detect BARD1 9’L RNA and methods of treatment of cancer using siRNA.
Long non-coding RNAs (lncRNAs) are ubiquitously expressed RNA molecules of more than 200 nucleotides without substantial ORFs. LncRNAs could act as epigenetic regulators of gene expression affecting transcription, mRNA stability and transport, and translation, although, precise functions have been attributed to only few of them. Competing endogenous RNAs (ceRNAs) represent one recently emerged type of functional lncRNAs that share microRNA recognition sequences with mRNAs and may compete for microRNA binding and thus affect regulation and function of target mRNAs. We studied the epigenetic regulation of the BARD1 gene. The BARD1 protein acts as tumor suppressor with BRCA1. In cancer, mRNAs encoding the tumor suppressor full length BARD1 are often down-regulated while the expression of oncogenic truncated isoforms is boosted. We found that the BARD1 3′UTR is almost 3000 nt long and harbors a large number of microRNA binding elements. In addition we discovered a novel lncRNA, BARD1 9′L, which is transcribed from an alternative promoter in intron 9 of the BARD1 gene and shares part of the 3′UTR with the protein coding BARD1 mRNAs. We demonstrate with the example of two microRNAs, miR-203 and miR-101, that they down-regulate the expression of FL BARD1 and cancer-associated BARD1 mRNAs, and that BARD1 9′L counteracts the effect of miR-203 and miR-101, As BARD1 9′L is abnormally over-expressed in human cancers, we suggest it might be a tumor promoting factor and treatment target.
