US 11,891,601 B2
Method to enhance the transcription regulation of SUPT4H on genes containing repetitive nucleotide sequences
Tzu-Hao Cheng, Taipei (TW); Chia-Rung Liu, Taipei (TW); Tse-I Lin, Taipei (TW); Yun-Yun Wu, Taipei (TW); and Stanley N. Cohen, Stanford, CA (US)
Assigned to NATIONAL YANG MING CHIAO TUNG UNIVERSITY, Taipei (TW)
Appl. No. 16/963,772
Filed by National Yang-Ming University, Taipei (TW)
PCT Filed Jan. 22, 2019, PCT No. PCT/CN2019/072597
§ 371(c)(1), (2) Date Jul. 21, 2020,
PCT Pub. No. WO2019/141279, PCT Pub. Date Jul. 25, 2019.
Claims priority of provisional application 62/620,308, filed on Jan. 22, 2018.
Prior Publication US 2021/0040479 A1, Feb. 11, 2021
Int. Cl. C12N 15/113 (2010.01); A61P 25/00 (2006.01); A61K 31/122 (2006.01); A61K 31/4745 (2006.01); A61K 31/7105 (2006.01)
CPC C12N 15/113 (2013.01) [A61K 31/122 (2013.01); A61K 31/4745 (2013.01); A61K 31/7105 (2013.01); A61P 25/00 (2018.01); C12N 2310/14 (2013.01); C12N 2320/31 (2013.01)] 12 Claims
 
1. A method of modulating expression of a gene containing expanded tri-nucleotide repeats in a cell, comprising:
administering to the cell a composition comprising an oligonucleotide that is complementary to a nucleic acid encoding SPT4 or SUPT4H, wherein the oligonucleotide is a siRNA, a shRNA, an antisense oligonucleotide, or a chemical reagent that is 6-chloropurine riboside; and
administering a compound that enhances R-loop formation, wherein the compound is selected from a topoisomerase inhibitor or an RNase H inhibitor,
wherein the gene contains a segment of DNA with CAG or CTG tri-nucleotide repeats that are prone to R-loop formation.