Methods and Compositions to Target and Treat Macrophages

Patent metadata

Field	Value
Publication number	US-2023241250-A1
Application number	US-202318163253-A
Country	US
Kind code	A1
Filing date	Feb 1, 2023
Priority date	Feb 1, 2022
Publication date	Aug 3, 2023
Grant date	—

Abstract

Provided herein are, in various embodiments, methods and compositions of inducing M2-like macrophage morphology. In certain embodiments, a composition comprising a polynucleotide encoding a ring finger protein 41 (RNF41) is contemplated. The disclosure also provides a method of preventing, treating, managing, and/or ameliorating tissue damage in a subject in need thereof. In some embodiments, the subject has chronic liver disease, chronic liver inflammation, chronic hepatic fibrosis, cirrhosis, or a combination thereof. In still further embodiments, the subject has undergone liver resection or liver transplantation.

First claim

What is claimed is:

1 . A method of inducing M2-like macrophage morphology in a macrophage, comprising contacting a macrophage with a composition, wherein the composition comprises a polynucleotide encoding a ring finger protein 41 (RNF41), under conditions whereby the composition enters the macrophage and RNF41 is expressed.

2 . The method of claim 1 , wherein the macrophage is a tumor-associated macrophage.

3 . The method of claim 1 , wherein the M2-like macrophage morphology consists of elevated expression of mannose receptor CD206, elevated production of matrix metalloproteinases, elevated collagenase activity, or a combination thereof.

4 . The method of claim 1 , wherein the macrophage has elevated anti-inflammatory factors, elevated anti-fibrotic factors, elevated pro-regenerative factors, or a combination thereof.

5 . The method of claim 1 , wherein the macrophage is in a subject, and the method comprises administering to the subject an effective amount of the composition, or a pharmaceutically acceptable salt thereof.

6 . The method of claim 1 , wherein the subject has, or is predisposed to have, tissue injury.

7 . The method of claim 6 , wherein the tissue is liver tissue, muscle tissue, lung tissue, spleen tissue, kidney tissue, a tissue of the mononuclear phagocyte system, or a combination thereof.

8 . The method of claim 5 , wherein the subject has chronic liver disease, liver failure, chronic liver inflammation, chronic hepatic fibrosis, cirrhosis, or a combination thereof.

9 . The method of claim 5 , wherein the subject has undergone a partial or complete hepatectomy, liver transplantation, or a combination thereof.

10 . The method of claim 6 , wherein tissue inflammation is reduced, tissue fibrosis is reduced, tissue repair is induced, or a combination thereof.

11 . The method of claim 6 , wherein hepatic fibrosis is reduced.

12 . The method of claim 6 , wherein hepatic regeneration is stimulated.

13 . A method of promoting hepatic regeneration in a subject in need thereof, the method comprising administering to the subject an effective amount of a composition comprising a polynucleotide encoding ring finger protein 41 (RNF41).

14 . The method of claim 13 , wherein the polynucleotide encoding RNF41 is a plasmid, wherein plasmid further comprises a promoter, wherein the promoter is CD11b.

15 . The method of claim 13 , wherein the plasmid is operably linked to a graphite nanoparticle by at least one PAMAM generation 5 dendrimer.

16 . The method of claim 13 , wherein the subject has or is predisposed to having cardiovascular disease, diabetes, an auto-immune disease, allergic asthma, inflammatory bowel disease, chronic hepatic and/or renal disease, malignancy, Alzheimer's disease, or a combination thereof.

17 . A composition comprising a polynucleotide encoding a ring finger protein 41 (RNF41), wherein the polynucleotide encoding RNF41 is a plasmid, and wherein the plasmid is operably linked to a graphite nanoparticle.

18 . The composition of claim 17 , wherein the plasmid further comprises a promoter, wherein the promoter is CD11b.

19 . The composition of claim 17 , wherein the plasmid is operably linked to the graphite nanoparticle.

20 . The composition of claim 19 , wherein the plasmid is operably linked to the graphite nanoparticle by at least one polyamidoamine (PAMAM) generation 5 dendrimer.

Assignees

• Massachusetts Inst Technology

Inventors

• Edelman Elazer R
• Melgar Lesmes Pedro

Classifications

• C12N15/87

  Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation · CPC title

• A61K48/0041

  the non-active part being polymeric · CPC title

• A61K48/005

  characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered · CPC title

• A61K48/0058 Primary

  Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct · CPC title

• A61K38/45

  Transferases (2) · CPC title