Nucleic acid sequences and methods for identifying compounds that affect RNA/RNA binding protein interactions and mRNA functionality
OwnerAnthony Giordano, Asish Xavierinventors
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Abstract
Disclosed herein are nucleic acid sequences and their optimized subfragments which are located in the mRNA untranslated regions of therapeutically-relevant genes. These sequences specifically bind RNA binding proteins (RBPs) and/or regulate the mRNA functionality. Also disclosed are methods of optimizing a subfragment of a parent nucleic acid sequence such that the RBP binding activity or mRNA functionality of the parent nucleic acid sequence is preserved in the optimized subfragment.
Claims11
A nucleic acid sequence comprising any one of the nucleic acid sequences of SEQ ID NOs 1-20, or a subfragment nucleic acid sequence derived from any one of the sequences of SEQ ID NOs 1-20, wherein an mRNA molecule comprising said sequence has RNA binding protein (RBP) binding activity or regulates the functionality of said mRNA.
A method of identifying an optimized subfragment of any one of the parent nucleic acid sequences of SEQ ID NOs 1-20, said method comprising isolating a subfragment nucleic acid sequence from said parent nucleic acid sequence, assaying RNA molecules comprising said subfragment for RBP binding activity or mRNA functionality, and identifying a subfragment nucleic sequence that maintains an RBP binding activity and/or mRNA functionality that is equivalent to said parent sequence.
A method of identifying a candidate compound having an effect on an RNA/RBP binding pair interaction or mRNA functionality, said method comprising contacting an RNA molecule comprising at least one nucleic acid sequence of any one of SEQ ID NOs 1-20, or at least one optimized subfragment sequence derived from any one of SEQ ID NOs 1-20, with at least one RBP, and at least one test compound, and measuring said RNA/RBP binding pair interaction and/or mRNA functionality, wherein a candidate compound is identified as a test compound that affects said interaction and/or functionality.
A method for identifying an RBP that interacts with an RNA molecule comprising the nucleic acid sequence of any one of SEQ ID NOs 1-20, or an optimized subfragment sequence of any one of SEQ ID NOs 1-20, said method comprising contacting said RNA molecule with at least one RBP, and measuring RNA/RBP binding pair interactions, wherein detection of said interactions identifies said RBP that interacts with said RNA molecule.
Dependencies are inferred from the claim text.