University of Pennsylvania

Regenxbio Inc.

Massachusetts Institute of Technology

University of Minnesota

Emory University

Swanbio Therapeutics Limited

Mcivor, R. Scott

Kozarsky, Karen

Belur, Lalitha R.

Karen Kozarsky

James M Wilson

Jerome Frank Strauss, Iii

Monty Krieger

Walter C Low

R Scott McIvor

Carolyn Ann Fairbanks

Attilio Rigotti

Lalitha R Belur

Anna P Tretiakova

Nicholas M Boulis

Sean Clark

Tugba Guven-Ozkan

Anthony Donsante

Jonathan Patrick Riley

Nicholas Matthew Boulis

Walter Low

R Scott Mcivor

A method to prevent, inhibit or treat one or more symptoms associated with a disease of the central nervous system by intrathecally, intracerebroventricularly or endovascularly administering a rAAV encoding a gene product associated with the disease, e.g., a mammal in which the gene product is absent or present at a reduced level relative to a mammal without the disease.

Methods to treat mucopolysaccharidosis type II or deficiency in iduronate-2-sulfatase using a recombinant adeno-associated virus (AAV) vector encoding iduronate-2-sulfatase

It is disclosed herein that ssAAV and scAAV vectors of the same serotype administered by injection into the cerebrospinal fluid (CSF) via the intracerebroventricular (ICV) or intrathecal (cisternal or lumbar) route exhibit different cellular tropisms in the central nervous system. Thus, a subject can be treated by injection into the CSF of ssAAV or scAAV vector encoding a therapeutic protein, such as an ssAAV9 or scAAV9 vector. The therapeutic protein can be targeted to specific cells using these vectors. In some embodiments, scAAV9 is utilized to achieve superior transduction in the hippocampus, cerebellum and cerebral cortex where both neurons, particularly Purkinje neurons, and glial cells (such as astrocytes) are transduced. In other embodiments, ssAAV9 is utilized to minimize transduction of astrocytes. In further embodiments, an immunosuppressive agent is also administered to the subject.

Injection of single-stranded or self-complementary adeno-associated virus 9 into the cerebrospinal fluid

The present disclosure generally relates to polynucleotides and AAV vectors that provide for the expression of ALD protein in target (e.g., neurons or glial) cells when administered to subjects in need thereof. The present disclosure further relates to compositions comprising such a polynucleotide or vector. These polynucleotides, vectors, and compositions may be used for the treatment and prevention of ALD or AMN in subjects in need thereof.

AAV-ABCD1 constructs and use for treatment or prevention of adrenoleukodystrophy (ALD) and/or adrenomyeloneuropathy (AMN)

Methods to treat mucopolysaccharide type I or deficiency in alpha-L-iduronidase using a recombinant adeno-associated virus encoding alpha-L-iduronidase

The invention provides a recombinant viral vector comprising the DNA of, or corresponding to, at least a portion of the genome of an adenovirus, which portion is capable of infecting a hepatic cell; and a human VLDL receptor gene operatively linked to regulatory sequences directing its expression. The vector is capable of expressing the normal VLDL receptor gene product in hepatic cells in vivo or in vitro. This viral vector is useful in the treatment of metabolic disorders caused by the accumulation of LDL in plasma, such as familial hypercholesterolemia or familial combined hyperlipidemia.

Methods and compositions for the treatment of defects in lipoprotein metabolism

Methods for regulation of lipid and cholesterol uptake are described which are based on regulation of the expression or function of the SR-BI HDL receptor. The examples demonstrate that estrogen dramatically downregulates SR-BI under conditions of tremendous upregulation of the LDL-receptor. The examples also demonstrate the upregulation of SR-BI in rat adrenal membranes and other non-placental steroidogenic tissues from animals treated with estrogen, but not in other non-placental non-steroidogenic tissues, including lung, liver, and skin. Examples further demonstrate the uptake of fluorescently labeled HDL into the liver cells of animal, which does not occur when the animals are treated with estrogen. Examples also demonstrate the in vivo effects of SR-BI expression on HDL metabolism, in mice transiently overexpressing hepatic SR-BI following recombinant adenovirus infection. Overexpression of the SR-BI in the hepatic tissue caused a dramatic decrease in cholesterol blood levels. These results demonstrate that modulation of SR-BI levels, either directly or indirectly, can be used to modulate levels of cholesterol in the blood.

Methods for modulation of cholesterol transport

The invention provides a recombinant viral vector comprising a human VLDL receptor gene operatively linked to regulatory sequences directing its expression. The vector is capable of expressing the normal VLDL receptor gene product in hepatic cells in vivo or in vitro. This viral vector is usefuil in the treatment of metabolic disorders caused by the accumulation of LDL in plasma, such as familial hypercholesterolemia or familial combined hyperlipidemia.

Methods and compositions for gene therapy for the treatment of defects in lipoprotein metabolism

Methods and compositions for gene therapy for the treatment of defects

Growing community of inventors

Bala Cynwyd, PA, United States of America

Karen Kozarsky