	US 12,419,915 B2
	Microglial progenitors for regeneration of functional microglia in the central nervous system and therapeutics uses thereof
Feng Zhang, Cambridge, MA (US)
Assigned to THE BROAD INSTITUTE, INC., Cambridge, MA (US); and MASSACHUSETTS INSTITUTE OF TECHNOLOGY, Cambridge, MA (US)
Appl. No. 17/437,485
Filed by THE BROAD INSTITUTE, INC., Cambridge, MA (US); and MASSACHUSETTS INSTITUTE OF TECHNOLOGY, Cambridge, MA (US)
PCT Filed Mar. 13, 2020, PCT No. PCT/US2020/022805 § 371(c)(1), (2) Date Sep. 9, 2021, PCT Pub. No. WO2020/186237, PCT Pub. Date Sep. 17, 2020.
Claims priority of provisional application 62/817,777, filed on Mar. 13, 2019.
Prior Publication US 2022/0152115 A1, May 19, 2022
Int. Cl. A61K 35/28 (2015.01); C12N 5/0789 (2010.01); C12N 5/079 (2010.01); C12N 9/22 (2006.01); C12N 15/11 (2006.01)

CPC A61K 35/28 (2013.01) [C12N 5/0622 (2013.01); C12N 5/0647 (2013.01); C12N 9/22 (2013.01); C12N 15/111 (2013.01); C12N 2310/20 (2017.05); C12N 2320/32 (2013.01); C12N 2506/11 (2013.01); C12N 2506/45 (2013.01); C12N 2510/00 (2013.01)]

20 Claims

1. A composition for treating or ameliorating a disease or disorder of a subject's central nervous system (CNS), comprising:

a cell population comprising stem cell-derived microglial cells genetically engineered to enhance CNS engraftment efficiency,

wherein the stem cell-derived microglial cells are genetically engineered:

to abrogate expression of CD26 and/or stromal cell-derived factor-1 genes, and one or more immunogenic genes chosen from OX40, GITR, 4-1BB, CD2, CD28, ICOS, CD27, HVEM, SLAM, CD226, PD1, CTLA4, LAG3, TIM3, B7-H1, PD-L1, TLT-2, CD30, CD160, BTLA, LAIR1, 2B4, CD244, TCR, PD-1, CTLA4, LAG-3, CCR5, PCSK9, APOC3, TRAC, TRBC, or any combination thereof, or

to abrogate expression of CD26 and/or stromal cell-derived factor-1 genes and induce the expression of one or more tolerogenic factors chosen from HLA-C, HLA-E, HLA-F, HLA-G, PD-L1, CTLA-4-Ig, CD47, CI-inhibitor, IL-35, HLA-A, HLA-B, or any combination thereof.