	US 12,421,517 B2
	Genetic modification of mammalian cells to confer resistance to CSF1R antagonists
Mathew Blurton-Jones, Irvine, CA (US); Jean Paul Chadarevian, Irvine, CA (US); Robert Spitale, Irvine, CA (US); Sunil Gandhi, Irvine, CA (US); Whitney England, Irvine, CA (US); Hayk Davtyan, Irvine, CA (US); and Jonathan Hasselmann, Irvine, CA (US)
Assigned to THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, Oakland, CA (US)
Filed by THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, Oakland, CA (US)
Filed on Dec. 21, 2022, as Appl. No. 18/069,543.
Application 18/069,543 is a continuation of application No. PCT/US2022/023139, filed on Apr. 1, 2022.
Claims priority of provisional application 63/236,951, filed on Aug. 25, 2021.
Claims priority of provisional application 63/169,578, filed on Apr. 1, 2021.
Prior Publication US 2023/0203500 A1, Jun. 29, 2023
Int. Cl. C12N 15/113 (2010.01); A61K 9/00 (2006.01); A61K 31/4439 (2006.01); A61K 31/444 (2006.01); A61K 31/713 (2006.01); A61K 35/30 (2015.01); C07K 14/715 (2006.01)

CPC C12N 15/1138 (2013.01) [A61K 9/0019 (2013.01); A61K 31/4439 (2013.01); A61K 31/444 (2013.01); A61K 31/713 (2013.01); A61K 35/30 (2013.01); C07K 14/7153 (2013.01); C12N 2310/14 (2013.01); C12N 2320/32 (2013.01)]

24 Claims

1. An isolated and modified human induced pluripotent stem cell (iPSC)-derived microglial cell comprising a polynucleotide comprising a nucleic acid sequence encoding a modified CSF1R protein that comprises a glycine-to-cysteine amino acid substitution at an amino acid residue corresponding to glycine 795 (G795C) of SEQ ID NO: 2, wherein the modified CSF1R protein:

(i) binds to ATP;

(ii) is activated by a CSF1R ligand that induces phosphorylation of the modified CSF1R protein; and

(iii) has a reduced sensitivity to a CSF1R inhibitor compared to a CSF1R protein consisting of the amino acid sequence of SEQ ID NO: 2.