US 12,281,314 B2
Methods and compositions for increasing protein expression and/or treating a haploinsufficiency disorder
Jeffery M. Coller, Novelty, OH (US); Thomas Sweet, Cleveland, OH (US); and Harvey Lodish, Cambridge, MA (US)
Assigned to CASE WESTERN RESERVE UNIVERSITY, Cleveland, OH (US); and WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH, Cambridge, MA (US)
Appl. No. 17/280,369
Filed by CASE WESTERN RESERVE UNIVERSITY, Cleveland, OH (US); and WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH, Cambridge, MA (US)
PCT Filed Sep. 26, 2019, PCT No. PCT/US2019/053268
§ 371(c)(1), (2) Date Mar. 26, 2021,
PCT Pub. No. WO2020/069199, PCT Pub. Date Apr. 2, 2020.
Claims priority of provisional application 62/736,847, filed on Sep. 26, 2018.
Prior Publication US 2022/0073933 A1, Mar. 10, 2022
Int. Cl. C12N 15/67 (2006.01); A61K 31/7088 (2006.01); A61K 45/06 (2006.01); A61K 48/00 (2006.01); A61P 43/00 (2006.01); C12N 15/11 (2006.01); C12N 15/86 (2006.01)
CPC C12N 15/67 (2013.01) [A61K 31/7088 (2013.01); A61K 45/06 (2013.01); A61K 48/0066 (2013.01); A61P 43/00 (2018.01); C12N 15/11 (2013.01); C12N 15/86 (2013.01); C12N 2750/14143 (2013.01)] 10 Claims
 
1. A method of increasing expression in a mammalian cell of a gene product encoded by a gene containing a first, second, and third non-optimal codon, the method comprising introducing into the cell an effective amount of a first, second, and third exogenous transfer RNA (tRNA) that each (i) comprises an anticodon that hybridizes to the first, second, and third non-optimal codon, respectively, and (ii) is capable of being aminoacylated with an amino acid, wherein introduction of the first, second, and third exogenous tRNAs into the cell increases the expression of the gene product relative to a similar cell lacking the first, second, and third exogenous tRNAs, and wherein the first, second, and/or third non-optimal codon is selected from ATA, GTA, and AGA.