Compositions and methods for improved RNA capture

A method for identifying a binding partner of a nucleic acid molecule of interest, the method comprising the steps of:

• a) contacting a complex comprising a target nucleic acid molecule with nucleic acid molecule comprising a duplex formed from hybridization of at least one protector oligonucleotide (PO) with at least one capture oligonucleotide (CO),
• wherein the CO comprises a 5′ toehold region, a central region, wherein the central region comprises a nucleotide sequence that is complementary to a nucleotide sequence of a target nucleic acid molecule and further comprises at least one modification, and a 3′ toehold region, and further wherein the 5′ toehold region of the CO comprises a nucleotide sequence that is complementary to a nucleotide sequence of the target nucleic acid molecule and wherein the 3′ toehold region of the CO comprises a nucleotide sequence that is complementary to a nucleotide sequence of the PO but not to the target nucleic acid molecule;
• and
• wherein the PO comprises a nucleotide sequence complementary to the central region and one of the 5′ toehold region and the 3′ toehold region of the CO, such that strand exchange occurs between the CO and the complex comprising a target nucleic acid molecule to form a CO:target complex;
• b) washing the CO:target complex;
• c) immunoprecipitating the CO:target complex;
• and
• d) eluting at least one component of the complex comprising the target nucleic acid molecule.