Amphiphilic block copolymers for nucleic acid delivery

Patent metadata

Field	Value
Publication number	US-9254258-B2
Application number	US-99132109-A
Country	US
Kind code	B2
Filing date	May 14, 2009
Priority date	May 15, 2008
Publication date	Feb 9, 2016
Grant date	Feb 9, 2016

Abstract

The present invention provides a composition comprising vesicles and encapsulated within the vesicles, nucleic acid comprising less than 1000 nucleotides, wherein the vesicles comprise an amphiphilic block copolymer having a hydrophilic and a hydrophobic block.
Methods of forming vesicles and methods of delivering nucleic acid, in particular, iRNA into cells, are also provided.

First claim

The invention claimed is:

1. A composition comprising nanovesicles and encapsulated within the aqueous core of the nanovesicles, nucleic acid comprising less than 1000 nucleotides, wherein the nanovesicles comprise an amphiphilic block copolymer having a hydrophilic block formed from 2-methacryloyloxy ethyl phosphorylcholine and a hydrophobic block formed from 2-(diisopropyl)amino ethyl methacrylate, wherein the degree of polymerisation of the hydrophilic block is about 20 to 25 and the degree of polymerisation of the hydrophobic block is about 70 to 75 and wherein the nucleic acid is siRNA.

2. A composition according to claim 1 , wherein the nanovesicles have a diameter in the range 50-1000 nm.

3. A composition according to claim 1 wherein the nucleic acid is small iRNA and comprises 15 to 25 nucleotide pairs.

4. A method for forming a composition according to claim 1 , wherein one of the blocks is pH sensitive, comprising the steps:
(i) dispersing the amphiphilic block copolymer in an organic solvent;
(ii) acidifying the pH of the composition formed in step (i);
(iii) adding the nucleic acid to the composition; and
(iv) raising the pH to around neutral to encapsulate the nucleic acid.

5. A method according to claim 4 comprising a preliminary step before step (i), wherein the amphiphilic block copolymer is dissolved in an organic solvent in a reaction vessel and the solvent is then evaporated to form a film on the inside of the reaction vessel.

6. An in vitro method of delivering nucleic acid comprising less than 1000 nucleotides into a cell comprising contacting a composition according to claim 1 with the cell.

7. A method of introducing nucleic acid comprising less than 1000 nucleotides into cells, comprising administering a composition according to claim 1 to a human or animal body.

8. A method of introducing nucleic acid comprising less than 1000 nucleotides into cells according to claim 7 , wherein a nucleic acid which is small iRNA and comprises 15 to 25 nucleotide pairs is delivered into a cell.

Assignees

• Lewis Andrew Lennard
• Battaglia Giuseppe
• Canton Irene
• Stratford Peter William
• Biocompatibles Uk Ltd

Inventors

• Lewis Andrew Lennard
• Battaglia Giuseppe
• Canton Irene
• Stratford Peter William

Classifications

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• C12N15/111

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

• C12N2320/32

  Special delivery means, e.g. tissue-specific · CPC title

• A61K48/0041

  the non-active part being polymeric · CPC title

• A61K9/1273 Primary

  Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances · CPC title