US 12,331,317 B2
Compositions and methods for increasing megakaryocyte production
Christopher Thom, Media, PA (US); Benjamin Voight, Philadelphia, PA (US); and Deborah French, Newark, DE (US)
Assigned to THE CHILDREN'S HOSPITAL OF PHILADELPHIA, Philadelphia, PA (US); and THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, Philadelphia, PA (US)
Appl. No. 17/604,954
Filed by THE CHILDREN'S HOSPITAL OF PHILADELPHIA, Philadelphia, PA (US); and THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, Philadelphia, PA (US)
PCT Filed Apr. 29, 2020, PCT No. PCT/US2020/030402
§ 371(c)(1), (2) Date Oct. 19, 2021,
PCT Pub. No. WO2020/223303, PCT Pub. Date Nov. 5, 2020.
Claims priority of provisional application 62/839,919, filed on Apr. 29, 2019.
Prior Publication US 2022/0177843 A1, Jun. 9, 2022
Int. Cl. C12N 5/078 (2010.01); A61K 35/19 (2015.01)
CPC C12N 5/0644 (2013.01) [A61K 35/19 (2013.01); C12N 2501/998 (2013.01); C12N 2506/45 (2013.01); C12N 2510/00 (2013.01)] 12 Claims
 
1. A method for producing megakaryocytes, said method comprising contacting stem cells with a tropomyosin 1 (TPM1) inhibitor and/or inactivating the TPM1 gene, thereby producing megakaryocytes,
wherein said TPM1 inhibitor is an inhibitory nucleic acid molecule selected from the group consisting of antisense, siRNA, and shRNA; and
wherein said inactivation of the TPM1 gene comprises delivering a gene editing system specific for the TPM1 gene to the cell.