	US 12,258,571 B2
	Methods and compositions for inducible expression of neurotrophic factors
Clive Svendsen, Pacific Palisades, CA (US); Joshua Breunig, Los Angeles, CA (US); and Aslam Akhtar, Torrance, CA (US)
Assigned to Cedars-Sinai Medical Center, Los Angeles, CA (US)
Appl. No. 16/979,640
Filed by CEDARS-SINAI MEDICAL CENTER, Los Angeles, CA (US)
PCT Filed Mar. 15, 2019, PCT No. PCT/US2019/022595 § 371(c)(1), (2) Date Sep. 10, 2020, PCT Pub. No. WO2019/178550, PCT Pub. Date Sep. 19, 2019.
Claims priority of provisional application 62/773,752, filed on Nov. 30, 2018.
Claims priority of provisional application 62/644,332, filed on Mar. 16, 2018.
Prior Publication US 2021/0024955 A1, Jan. 28, 2021
Int. Cl. C12N 15/86 (2006.01); A61K 31/65 (2006.01); A61K 35/30 (2015.01); A61K 38/18 (2006.01); C07K 14/475 (2006.01); C12N 5/079 (2010.01)

CPC C12N 15/86 (2013.01) [A61K 31/65 (2013.01); A61K 35/30 (2013.01); A61K 38/185 (2013.01); C07K 14/4756 (2013.01); C12N 5/0618 (2013.01); C12N 2506/45 (2013.01); C12N 2830/003 (2013.01); C12N 2830/205 (2013.01)]

19 Claims

1. A method of increasing glial derived neurotrophic factor (GDNF) levels in the central nervous system of an individual afflicted with a neurodegenerative disorder, the method comprising:

administering to the central nervous system of the individual a plurality of induced pluripotent stem cell derived neural progenitor cells (iNPCs), wherein the iNPCs express a genomically integrated expression cassette comprising, in a single piggyBac vector:

a constitutive promoter driving constitutive expression of rTA transactivator,

an inducible, bi-directional polycistronic promoter comprising a tet response element, and

a sequence encoding GDNF, wherein GDNF expression is inducible and reversible in the individual administered with the iNPCs; and

administering to the individual a tetracycline-class antibiotic, wherein the tetracycline-class antibiotic leads to increased GDNF levels in the central nervous system of the individual.