US 12,264,344 B2
Protein/oligonucleotide core-shell nanoparticle therapeutics
Chad A. Mirkin, Wilmette, IL (US); and Jeffrey D. Brodin, Evanston, IL (US)
Assigned to Northwestern University, Evanston, IL (US)
Appl. No. 15/502,955
Filed by Northwestern University, Evanston, IL (US)
PCT Filed Aug. 19, 2015, PCT No. PCT/US2015/045971
§ 371(c)(1), (2) Date Feb. 9, 2017,
PCT Pub. No. WO2016/028940, PCT Pub. Date Feb. 25, 2016.
Claims priority of provisional application 62/137,183, filed on Mar. 23, 2015.
Claims priority of provisional application 62/039,608, filed on Aug. 20, 2014.
Claims priority of provisional application 62/039,340, filed on Aug. 19, 2014.
Prior Publication US 2017/0232109 A1, Aug. 17, 2017
Int. Cl. C12N 9/96 (2006.01); A61K 38/43 (2006.01); A61K 38/44 (2006.01); A61K 38/47 (2006.01); A61K 47/54 (2017.01); A61K 47/69 (2017.01); C07K 19/00 (2006.01); C12N 9/08 (2006.01); C12N 9/38 (2006.01); C12P 3/00 (2006.01); C12P 19/02 (2006.01); C12P 19/14 (2006.01); B82Y 5/00 (2011.01)
CPC C12N 9/2471 (2013.01) [A61K 38/44 (2013.01); A61K 38/47 (2013.01); A61K 47/549 (2017.08); A61K 47/6921 (2017.08); C07K 19/00 (2013.01); C12N 9/0065 (2013.01); C12N 9/96 (2013.01); C12P 3/00 (2013.01); C12P 19/02 (2013.01); C12P 19/14 (2013.01); C12Y 111/01006 (2013.01); C12Y 302/01023 (2013.01); B82Y 5/00 (2013.01); Y02P 20/582 (2015.11)] 21 Claims
OG exemplary drawing
 
1. A method of inhibiting expression of a gene product encoded by a target polynucleotide comprising:
contacting a target polynucleotide with a nanoparticle comprising a core, a plurality of polynucleotides comprising a shell, and a linker,
wherein the linker connects the core to at least one polynucleotide of the plurality of polynucleotides comprising the shell and comprises:
Formula (I), (II), or both:

OG Complex Work Unit Chemistry
L and L2 are each independently selected from C1-10 alkylene, —C(O)—C1-10 alkylene-Y— and —C(O)—C1-10 alkylene-Y—C1-10 alkylene-(OCH2CH2)m-Y—;
each Y is independently selected from the group consisting of a bond, C(O), O, NH, C(O)NH, and NHC(O);
m is 0, 1, 2, 3, 4, or 5; and
PN is the at least one polynucleotide of the plurality of polynucleotides comprising the shell,
wherein the core is a single protein,
wherein the single protein exhibits catalytic activity, the single protein does not exhibit transport activity and the single protein is not albumin,
wherein the plurality of polynucleotides comprising the shell are attached to the surface of the single protein via covalent bonds at a surface density of at least 10 pmol/cm2,
wherein at least one polynucleotide of the plurality of polynucleotides comprising the shell is attached to the single protein surface via a surface amino group from a lysine residue of the single protein,
wherein at least one polynucleotide of the plurality of polynucleotides is sufficiently complementary to the target polynucleotide to hybridize under conditions sufficient to inhibit expression of the gene product by at least 10%, and
wherein at least one polynucleotide of the plurality of polynucleotides is 5 to 40 nucleotides in length.