	US 11,872,195 B2
	Compositions and methods to program therapeutic cells using targeted nucleic acid nanocarriers
Matthias Stephan, Seattle, WA (US); and Howell F. Moffett, Seattle, WA (US)
Assigned to Fred Hutchinson Cancer Center, Seattle, WA (US)
Filed by FRED HUTCHINSON CANCER CENTER, Seattle, WA (US)
Filed on Dec. 17, 2018, as Appl. No. 16/222,942.
Application 16/222,942 is a division of application No. 15/594,344, filed on May 12, 2017, granted, now 10,188,749, issued on Jan. 29, 2019.
Application 15/594,344 is a continuation of application No. PCT/US2017/027767, filed on Apr. 14, 2017.
Claims priority of provisional application 62/442,890, filed on Jan. 5, 2017.
Claims priority of provisional application 62/322,581, filed on Apr. 14, 2016.
Prior Publication US 2019/0111153 A1, Apr. 18, 2019
Int. Cl. A61K 48/00 (2006.01); C12N 9/22 (2006.01); C07K 14/705 (2006.01); C12N 15/88 (2006.01); A61K 35/14 (2015.01)

CPC A61K 48/005 (2013.01) [C07K 14/705 (2013.01); C12N 9/22 (2013.01); C12N 15/88 (2013.01); A61K 35/14 (2013.01)]

19 Claims

1. A method of selectively modifying a selected cell population of hematopoietic origin in vivo, the method comprising:

i) adding 12 kDa to 18 kDa polyglutamic acid (PGA) conjugated to selected cell targeting ligands that bind the selected cell population of hematopoietic origin to a first solution comprising nucleic acid encapsulated within poly(β-amino ester) (PBAE) to form a second solution; and

ii) incubating the second solution wherein selected cell-targeted synthetic nanocarriers form within 5 minutes of the adding and comprise

A) the nucleic acid encapsulated within the PBAE;

B) a coating comprising the PGA on the outer surface of the PBAE; and

C) the selected cell targeting ligands extending from the outer surface of the coating and conjugated to the PGA within the coating; and

iii) administering the formed selected cell-targeted synthetic nanocarriers to a subject comprising the selected cell population of hematopoietic origin, thereby selectively modifying the selected cell population of hematopoietic origin in vivo.