Biocompatible infinite coordination polymer nanoparticle-nucleic acid conjugates for antisense gene regulation

Patent metadata

Field	Value
Publication number	US-9617541-B2
Application number	US-201514831316-A
Country	US
Kind code	B2
Filing date	Aug 20, 2015
Priority date	Aug 20, 2014
Publication date	Apr 11, 2017
Grant date	Apr 11, 2017

Abstract

Disclosed herein are metal-ligand complexes containing polynucleotides, compounds for making the same, and methods of using the same.

First claim

What is claimed is:

1. A compound having a structure

wherein
L is C 1-20 alkylene or —C(O)NH—C 1-20 alkylene; and
n is 1 or 2.

2. The compound of claim 1 , wherein n is 1.

3. The compound of claim 2 , wherein the pyridone moiety is attached to the phenyl at the para position.

4. The compound of claim 1 , wherein n is 2.

5. The compound of claim 4 , wherein the pyridone moieties are attached to the phenyl at each meta position.

6. The compound of claim 1 , wherein L is C 1-20 alkylene.

7. The compound of claim 1 , wherein L is —C(O)NH—C 1-20 alkylene.

8. A polynucleotide comprising at a terminus a moiety comprising:

wherein
L is C 1-20 alkylene or —C(O)NH—C 1-20 alkylene; and
n is 1 or 2.

9. The polynucleotide of claim 8 , wherein n is 1.

10. The polynucleotide of claim 8 , wherein n is 2, and the pyridone moieties are attached to the phenyl at each meta position.

11. The polynucleotide of claim 8 , wherein the terminus of the polynucleotide has a structure:

or a mixture thereof,
L 2 is C 1-10 alkylene, —C(O)—C 1-10 alkylene-Y—, and —C(O)—C 1-10 alkylene-Y—C 1-10 alkylene-(OCH 2 CH 2 ) m —Y—;
each Y is independently selected from the group consisting of a bond, C(O), O, NH, C(O)NH, and NHC(O); and
m is 0, 1, 2, 3, 4, or 5.

12. A metal-ligand complex comprising the polynucleotide of claim 8 and Fe(III).

13. A metal-ligand complex comprising the compound of claim 1 and Fe(III).

14. The metal-ligand complex of claim 13 in the form of an infinite coordination polymer having a repeating formula of Fe 2 (Compound) 3 .

15. The metal-ligand complex of claim 13 , further comprising a polynucleotide covalently attached via an alkyne moiety on the polynucleotide to the azide moiety on the compound to form a triazole linkage.

16. A method of inhibiting expression of a gene product encoded by a target polynucleotide comprising contacting the target polynucleotide with the metal-ligand complex of claim 15 to inhibit expression of the gene product.

Assignees

• Univ Northwestern

Inventors

• Mirkin Chad A
• Calabrese Colin Michael
• Briley William E
• Merkel Timothy J

Classifications

• B82Y15/00

  Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors · CPC title

• C12N2310/351

  Conjugate · CPC title

• C12N15/111

  General methods applicable to biologically active non-coding nucleic acids · CPC title

• C12N2310/11

  Antisense · CPC title

• C12N15/113 Primary

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title