US 12,359,199 B2
Regulation of gene expression via aptamer-mediated control of self-cleaving ribozymes
Michael J. Volles, Cambridge, MA (US); Olivier F. Danos, New York, NY (US); Alex R. Boyne, Jersey City, NJ (US); Veronique Zennou, Jersey City, NJ (US); and Xuecui Guo, Oyster Bay, NY (US)
Assigned to MeiraGTX UK II Limited, London (GB)
Filed by MEIRAGTX UK II LIMITED, London (GB)
Filed on Nov. 29, 2022, as Appl. No. 18/059,606.
Application 18/059,606 is a division of application No. 16/074,681, granted, now 11,512,310, issued on Nov. 29, 2022, previously published as PCT/US2017/016303, filed on Feb. 2, 2017.
Claims priority of provisional application 62/290,187, filed on Feb. 2, 2016.
Claims priority of provisional application 62/290,209, filed on Feb. 2, 2016.
Prior Publication US 2023/0220382 A1, Jul. 13, 2023
Int. Cl. C12N 15/11 (2006.01); C12N 15/113 (2010.01); C12N 15/115 (2010.01); C12N 15/86 (2006.01)
CPC C12N 15/111 (2013.01) [C12N 15/113 (2013.01); C12N 15/115 (2013.01); C12N 15/86 (2013.01); C12N 2310/12 (2013.01); C12N 2310/121 (2013.01); C12N 2310/16 (2013.01); C12N 2310/3519 (2013.01); C12N 2830/50 (2013.01); C12N 2830/52 (2013.01)] 25 Claims
 
1. A polynucleotide construct for reducing the expression of a target gene in response to an aptamer ligand, the polynucleotide construct comprising (a) the target gene coding sequence flanked by a 5′ and a 3′ untranslated region (UTR); and (b) a riboswitch that comprises a twister ribozyme linked by a stem to an aptamer; wherein the aptamer comprises at least one stem; wherein the stem sequence linking the twister ribozyme to the aptamer comprises sequence that forms the aptamer stem and the P3 stem of the twister ribozyme; and wherein the target gene is linked to the P1 stem of the twister ribozyme; and wherein the riboswitch is located in (i) the 5′ UTR, (ii) the 3′ UTR, or (iii) the target gene coding sequence, 3′ of the start codon.