Programmable polypeptide and nucleic acid nanoparticles

Patent metadata

Field	Value
Publication number	US-10407469-B2
Application number	US-201715476083-A
Country	US
Kind code	B2
Filing date	Mar 31, 2017
Priority date	Apr 1, 2016
Publication date	Sep 10, 2019
Grant date	Sep 10, 2019

Abstract

Provided herein are polypeptides that self-assemble into nanoparticles upon binding to nucleic acids. The nanoparticles find use, for example in the delivery of the nucleic acids into cells.

First claim

The invention claimed is:

1. A polypeptide comprising an assembly domain and a nucleic-acid-binding domain (NABD),
wherein the assembly domain comprises an amino acid sequence selected from the group consisting of: SEQ ID NO:2 and SEQ ID NO:12; and
wherein upon binding of the NABD to a nucleic acid to form a polypeptide/nucleic acid complex, the assembly domain facilitates self-assembly of the polypeptide/nucleic acid complex into nanoparticles.

2. The polypeptide of claim 1 , wherein the amino acid sequence comprises SEQ ID NO:2.

3. The polypeptide of claim 2 , wherein the amino acid sequence comprises SEQ ID NO:1.

4. The polypeptide of claim 2 , wherein the amino acid sequence comprises SEQ ID NO:5.

5. The polypeptide of claim 1 , wherein the amino acid sequence comprises SEQ ID NO:12.

6. The polypeptide of claim 5 , wherein the amino acid sequence comprises SEQ ID NO:11.

7. The polypeptide of claim 1 , wherein the NABD binds single-stranded (ss) and/or double-stranded DNA and/or RNA.

8. The polypeptide of claim 1 , wherein the NABD and assembly domain are connected by a linker moiety.

9. The polypeptide of claim 1 , further comprising a bioactive domain that enhances one or more characteristics selected from the group consisting of cell internalization, cell-targeting, endosome escape, and nuclear delivery.

10. The polypeptide of claim 9 , wherein the bioactive domain is selected from the group consisting of SEQ ID NO: 6, SEQ ID NO: 8, and SEQ ID NO: 10.

11. A carrier nanoparticle comprising: (a) cargo nucleic acids, and (b) polypeptides of claim 1 .

12. The carrier nanoparticle of claim 11 , wherein the cargo nucleic acid is a single stranded or double stranded DNA or RNA.

13. The carrier nanoparticle of claim 11 , wherein binding of the polypeptide to the cargo nucleic acid facilitates self-assembly of the polypeptide/nucleic acid complexes into the carrier nanoparticles.

14. The carrier nanoparticle of claim 11 , wherein the nanoparticle is between 20 and 800 nm in diameter.

15. A method of delivering a cargo nucleic acid into a cell, comprising exposing the cell to a nanoparticle of claim 11 .

Assignees

• Univ Northwestern

Inventors

• Hernandez-Garcia Armando
• Stupp Samuel I
• Alvarez Pinto Zaida

Classifications

• C07K2319/735

  containing a domain for self-assembly, e.g. a viral coat protein (includes phage display) · CPC title

• C07K2319/10

  containing a tag for extracellular membrane crossing, e.g. TAT or VP22 · CPC title

• C07K2319/09

  containing a nuclear localisation signal · CPC title

• C07K14/4723

  Cationic antimicrobial peptides, e.g. defensins · CPC title

• C12N2310/3517

  Marker; Tag · CPC title