US 12,391,948 B2
RNA-regulated fusion proteins and methods of their use
Samie R. Jaffrey, New York, NY (US); and Jiahui Wu, New York, NY (US)
Assigned to CORNELL UNIVERSITY, Ithaca, NY (US)
Appl. No. 17/637,940
Filed by CORNELL UNIVERSITY, Ithaca, NY (US)
PCT Filed Aug. 31, 2020, PCT No. PCT/US2020/048781
§ 371(c)(1), (2) Date Feb. 24, 2022,
PCT Pub. No. WO2021/042050, PCT Pub. Date Mar. 4, 2021.
Claims priority of provisional application 62/894,651, filed on Aug. 30, 2019.
Prior Publication US 2022/0290161 A1, Sep. 15, 2022
Int. Cl. C12N 15/62 (2006.01); A61K 31/7105 (2006.01); C07K 19/00 (2006.01); C12N 5/071 (2010.01); C12N 9/02 (2006.01); C12N 15/115 (2010.01); C12N 15/52 (2006.01); C12N 15/85 (2006.01); C12Q 1/6816 (2018.01)
CPC C12N 15/62 (2013.01) [C12N 5/0602 (2013.01); C12N 15/115 (2013.01); C12N 15/52 (2013.01); C12N 15/85 (2013.01); C12Q 1/6816 (2013.01); C12Y 111/01011 (2013.01); C12Y 113/12013 (2013.01); C12Y 201/01043 (2013.01); C12Y 603/0401 (2013.01); C07K 2319/60 (2013.01); C07K 2319/61 (2013.01); C07K 2319/85 (2013.01); C12N 2310/16 (2013.01); C12N 2800/107 (2013.01)] 10 Claims
 
1. A nucleic acid molecule encoding an RNA-regulated fusion protein, said nucleic acid molecule comprising:
a first nucleic acid sequence encoding a protein of interest and a second nucleic acid sequence encoding an RNA-regulated destabilization domain,
wherein the second nucleic acid sequence is operably coupled to the first nucleic acid sequence,
wherein the RNA-regulated destabilization domain is a bifunctional peptide comprising:
a lentiviral transactivator of transcription (Tat) peptide and
a degron peptide,
wherein an RNA aptamer interacts with the RNA-regulated destabilization domain to stabilize the protein of interest, and
wherein the RNA-regulated destabilization domain is tDeg as set forth in SEQ ID NO: 63.