Methods of improving adeno-associated viral transduction
Described herein are saturating agents, AAV gene therapy vectors, and therapeutic agents, as well as methods and kits comprising the same.
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 comprising soybean oil, egg yolk phospholipids, glycerine, and water, wherein the saturating agent is taken up by the reticuloendothelial system (RES), wherein transduction efficiency of the AAV gene therapy vector is increased at least 3 fold for 35 days post administration compared to the transduction efficiency in the absence of the saturating agent.
2. The method according to claim 1 , wherein the saturating agent is selected from the group consisting of:
(a) a saturating agent comprising 10% soybean oil, 1.2% egg yolk phospholipids, 2.25% glycerin, and water;
(b) a saturating agent comprising 20% soybean oil, 1.2% egg yolk phospholipids, 2.25% glycerin, and water; and
(c) a saturating agent comprising 30% soybean oil, 1.2% egg yolk phospholipids, 2.25% glycerin, and water.
3. 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.
4. 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.
5. The method according to claim 1 , wherein the AAV gene therapy vector is administered via the bloodstream.
6. The method according to claim 1 , wherein the treatment is of the liver of the human subject.
7. 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 syndrome, Niemann-Pick, Krabbe disease, hemophilia A, hemophilia B, Huntington's disease (HD) and cardiac disease.
8. The method according to claim 7 , for the treatment of a disease selected from haemophilia A, haemophilia B, and Huntington's disease (HD).