Enhancing Translation of LINE-1 Encoded ORF2p for Cancer Therapeutics

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Unmet Need

A substantial portion (~50%) of human malignancies overexpress a protein encoded by a genomic repeat, the Long INterspersed Element-1 (LINE-1)-encoded ORF1p. These include colon, pancreatic, lung, ovarian, breast and prostate cancers. LINE-1 is a retrotransposon that codes for both RNA and proteins which in turn function to make more genomic copies of the sequence. LINE-1 is one of the most prevalent repeats in the human genome, making up ~20% of our DNA. LINE-1 is transcribed as a bi-cistronic RNA which encodes an RNA binding protein, open reading frame 1 protein (ORF1p), and a protein with endonuclease (EN) and reverse transcriptase (RT) activities, ORF2p. We need targeted ways to treat LINE-1 ORF1p(+) cancers.


Technology Overview

Hopkins researchers have shown that ORF2p is not expressed at appreciable levels in ORF1p(+) tumors, and that its expression is a potent, dose-dependent inhibitor of cell growth, sensitizes cells to DNA-damaging chemotherapies, and has immunological effects. Moreover, they have shown that cells actively suppress ORF2p translation from the bi-cistronic LINE-1 RNA, thus avoiding overexposure to this genotoxic protein.

The proposed invention enhances ORF2p translation by using small molecules targeting these pathways or trans-acting RNAs as therapeutic agents in ORF1p(+) human cancers. 


Stage of Development

In vitro demonstration of ORF2p upregulation. Drug platforms under development.



Patent Information:
Title App Type Country Serial No. Patent No. File Date Issued Date Expire Date Patent Status
ENHANCING EXPRESSION OF LINE-1 ENCODED ORF2P FOR CANCER THERAPEUTICS PCT: Patent Cooperation Treaty PCT PCT/US2020/067060   12/26/2020     Pending
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