US 11,866,736 B2
Protein prostheses for mitochondrial diseases or conditions
Vamsi Mootha, Boston, MA (US); Denis Titov, Boston, MA (US); Valentin Cracan, Boston, MA (US); and Zenon Grabarek, Boston, MA (US)
Assigned to The General Hospital Corporation, Boston, MA (US)
Appl. No. 15/749,218
Filed by The General Hospital Corporation, Boston, MA (US)
PCT Filed Aug. 1, 2016, PCT No. PCT/US2016/045015
§ 371(c)(1), (2) Date Jan. 31, 2018,
PCT Pub. No. WO2017/023855, PCT Pub. Date Feb. 9, 2017.
Claims priority of provisional application 62/199,695, filed on Jul. 31, 2015.
Prior Publication US 2019/0017034 A1, Jan. 17, 2019
Int. Cl. C12N 9/02 (2006.01); C12N 5/10 (2006.01); C07K 14/335 (2006.01); C07K 14/195 (2006.01); C12N 5/071 (2010.01); C12N 15/52 (2006.01); C12N 15/85 (2006.01); A61K 47/66 (2017.01); A61P 25/16 (2006.01); A61K 9/127 (2006.01); A61K 38/16 (2006.01); A61K 38/17 (2006.01); A61K 47/18 (2017.01); A61K 47/42 (2017.01); C12N 15/113 (2010.01); C12N 15/62 (2006.01)
CPC C12N 9/0036 (2013.01) [C07K 14/195 (2013.01); C07K 14/335 (2013.01); C12N 5/0602 (2013.01); C12N 5/10 (2013.01); C12N 15/52 (2013.01); C12N 15/85 (2013.01); C12Y 106/03001 (2013.01); A61K 9/127 (2013.01); A61K 38/162 (2013.01); A61K 38/1709 (2013.01); A61K 38/1774 (2013.01); A61K 47/18 (2013.01); A61K 47/42 (2013.01); A61K 47/66 (2017.08); A61P 25/16 (2018.01); C07K 2319/07 (2013.01); C07K 2319/43 (2013.01); C12N 15/113 (2013.01); C12N 15/62 (2013.01)] 5 Claims
 
1. A mammalian cell comprising a nucleic acid encoding a water-forming NADH oxidase bound to a targeting peptide that localizes the water-forming NADH oxidase to mitochondria, wherein the water-forming NADH oxidase comprises an NADH-binding site comprising (i) a Rossmann fold domain having a dinucleotide-binding motif defined by the peptide G-x-G-x-x-G/A, wherein each x represents any amino acid, and (ii) a cofactor specificity loop, wherein the water-forming NADH oxidase is a bacterial water-forming NADH oxidase.