Methods of improving adeno-associated viral transduction

Patent metadata

Field	Value
Publication number	US-2020360535-A1
Application number	US-202016896811-A
Country	US
Kind code	A1
Filing date	Jun 9, 2020
Priority date	Dec 22, 2017
Publication date	Nov 19, 2020
Grant date	—

Abstract

Described herein are saturating agents, AAV gene therapy vectors, and therapeutic agents, as well as methods and kits comprising the same.

First claim

1 . A method of treating a human subject, comprising administering an adeno-associated virus (AAV) gene therapy vector to a human subject having been administered a saturating agent, wherein the saturating agent is taken up by the reticuloendothelial system (RES).

2 . The method according to claim 1 , wherein the saturating agent comprises one or more nutrients selected from the group consisting of carbohydrates, amino acids, lipids, vitamins, dietary minerals, and combinations thereof.

3 . The method according to claim 1 , wherein the saturating agent comprises one or more lipids selected from the group consisting of triglycerides, steroids, phospholipids, and combinations thereof.

4 . The method according to claim 1 , wherein the saturating agent comprises an emulsion.

5 . The method according to claim 4 , wherein the emulsion is a lipid and/or a fat emulsion.

6 . The method according to claim 1 , wherein the saturating agent is selected from the group consisting of INTRALIPID® 10%, INTRALIPID® 20%, and INTRALIPID® 30%.

7 . The method according to claim 1 , wherein the saturating agent comprises triglycerides, and wherein the plasma concentration of triglycerides in the blood of the human subject is at least 3 mmol/L prior to administration of the AAV gene therapy vector.

8 . The method according to claim 1 , wherein the saturating agent has been administered to the human subject at least 15 minutes or more prior to administration of the AAV gene therapy vector.

9 . The method according to claim 1 , wherein the AAV gene therapy vector is administered via the bloodstream.

10 . The method according to claim 1 , wherein the treatment is of the liver of the human subject.

11 . The method according to claim 1 , for the treatment of a disease selected from the group consisting of acute intermittent porphyria (AIP), age-related macular degeneration, Alzheimer's disease, arthritis, Batten disease, Canavan disease, Citrullinemia type 1, Crigler Najjar, congestive heart failure, cystic fibrosis, Duchene muscular dystrophy, dyslipidemia, glycogen storage disease type I (GSD-I), hemophilia A, hemophilia B, hereditary emphysema, homozygous familial hypercholesterolemia (HoFH), Huntington's disease (HD), Leber's congenital amaurosis, methylmalonic academia, ornithine transcarbamylase deficiency (OTC), Parkinson's disease, phenylketonuria (PKU), spinal muscular atrophy, paralysis, Wilson disease, epilepsy, Pompe disease, amyotrophic lateral sclerosis (ALS), Tay-Sachs disease, hyperoxaluria (PH-1), spinocerebellar ataxia type 1 (SCA-1), SCA-3, u-dystrophin, Gaucher's types II or III, arrhythmogenic right ventricular cardiomyopathy (ARVC), Fabry disease, familial Mediterranean fever (FMF), proprionic acidemia, fragile X syndrome, Rett sundrome, Niemann-Pick, Krabbe disease, hemophilia A, hemophilia B, Huntington's disease (HD) and cardiac disease.

Assignees

• Uniqure Ip Bv

Inventors

• Ferreira Valerie

Classifications

• C12N15/86 Primary

  Viral vectors · CPC title

• A61K9/107

  Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} · CPC title

• A61K35/76

  Viruses; Subviral particles; Bacteriophages · CPC title

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title

• C12N2750/14143

  viral genome or elements thereof as genetic vector · CPC title