Abstract: 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.
Type:
Application
Filed:
November 7, 2023
Publication date:
April 4, 2024
Applicants:
Emory University, REGENXBIO Inc.
Inventors:
Anthony Donsante, Karen Kozarsky, Nicholas Matthew Boulis, Jonathan Patrick Riley
Abstract: Compositions and methods are described for the delivery of a fully human-glycosylated (HuGly) ?-L-iduronidase (IDUA) to the cerebrospinal fluid of the central nervous system (CNS) of a human subject diagnosed with mucopolysaccharidosis I (MPS I).
Type:
Application
Filed:
October 3, 2023
Publication date:
February 15, 2024
Applicant:
REGENXBIO Inc.
Inventors:
Stephen Yoo, Rickey Robert Reinhardt, Curran Matthew Simpson, Zhuchun Wu
Abstract: Compositions and methods are described for the delivery of recombinant human iduronate-2-sulfatase (IDS) produced by human neuronal or glial cells to the cerebrospinal fluid of the central nervous system (CNS) of a human subject diagnosed with mucopolysaccharidosis II (MPS II).
Type:
Grant
Filed:
April 13, 2018
Date of Patent:
March 28, 2023
Assignee:
REGENXBIO Inc.
Inventors:
Stephen Yoo, Rickey Robert Reinhardt, Curran Matthew Simpson, Zhuchun Wu
Abstract: Compositions and methods are described for the delivery of a fully human post-translationally modified (HuPTM) monoclonal antibody (“mAb”) or the antigen-binding fragment of a mAb against human vascular endothelial growth factor (“hVEGF”)—such as, e.g., a fully human-glycosylated (HuGly) anti-hVEGF antigen-binding fragment—to the retina/vitreal humour in the eye(s) of human subjects diagnosed with ocular diseases caused by increased neovascularization, for example, neovascular age-related macular degeneration (“nAMD”), also known as “wet” age-related macular degeneration (“WAMD”), age-related macular degeneration (“AMD”), and diabetic retinopathy.
Type:
Application
Filed:
March 25, 2022
Publication date:
February 23, 2023
Applicant:
REGENXBIO Inc.
Inventors:
Curran Matthew Simpson, Stephen Yoo, Karen Fran Kozarsky, Rickey Robert Reinhardt, Laura A. Coruzzi
Abstract: Compositions and methods are described for the delivery of therapeutic products (such as therapeutic proteins (for example, antibodies), therapeutic RNAs (for example, shRNAs, siRNAs, and miRNAs), and therapeutic aptamers) to the retina/vitreal humour in the eyes of human subjects to treat pathologies of the eye, involving, for example, recombinant viral vectors such as recombinant adeno-associated virus (rAAV) vectors.
Type:
Application
Filed:
April 2, 2020
Publication date:
May 12, 2022
Applicant:
REGENXBIO, Inc.
Inventors:
Olivier Danos, Sherri Van Everen, Jesse I. Yoo, Samir Maganbhai Patel, Avanti Arvind Ghanekar, Anthony Ray O'Berry, Kim Rees Irwin-Pack, Darin Thomas Curtiss
Abstract: Provided herein are formulations comprising recombinant AAV particles. In some embodiments, the formulation is a frozen formulation or a lyophilized formulation. Also provided herein are methods for reducing rAAV genome release from rAAV particles.
Type:
Application
Filed:
April 17, 2020
Publication date:
May 12, 2022
Applicant:
REGENXBIO Inc.
Inventors:
Tristan James Marshall, Jared Bee, Yu Zhang, Roberto DePaz
Abstract: Compositions and methods are described for the delivery of recombinant human iduronate-2-sulfatase (IDS) produced by human neuronal or glial cells to the cerebrospinal fluid of the central nervous system (CNS) of a human subject diagnosed with mucopolysaccharidosis II (MPS II).
Type:
Application
Filed:
April 13, 2018
Publication date:
May 14, 2020
Applicant:
REGENXBIO INC.
Inventors:
Stephen Yoo, Rickey Robert Reinhardt, Curran Matthew Simpson, Zhuchun Wu
Abstract: Compositions and methods are described for the delivery of a fully human-glycosylated (HuGly) ?-L-iduronidase (IDUA) to the cerebrospinal fluid of the central nervous system (CNS) of a human subject diagnosed with mucopolysaccharidosis I (MPS I).
Type:
Application
Filed:
January 30, 2018
Publication date:
November 28, 2019
Applicant:
REGENXBIO Inc.
Inventors:
Stephen Yoo, Rickey Robert Reinhardt, Curran Matthew Simpson, Zhuchun Wu
Abstract: Compositions and methods are described for the delivery of a fully human post-translationally modified (HuPTM) monoclonal antibody (“mAb”) or the antigen-binding fragment of a mAb against human vascular endothelial growth factor (“hVEGF”)—such as, e.g., a fully human-glycosylated (HuGly) anti-hVEGF antigen-binding fragment—to the retina/vitreal humour in the eye(s) of human subjects diagnosed with ocular diseases caused by increased neovascularization, for example, neovascular age-related macular degeneration (“nAMD”), also known as “wet” age-related macular degeneration (“WAMD”), age-related macular degeneration (“AMD”), and diabetic retinopathy.
Type:
Application
Filed:
March 22, 2019
Publication date:
July 11, 2019
Applicant:
REGENXBIO Inc.
Inventors:
Curran Matthew Simpson, Stephen Yoo, Karen Fran Kozarsky, Rickey Robert Reinhardt, Laura A. Coruzzi
Abstract: Compositions and methods are described for the delivery of a fully human post-translationally modified (HuPTM) monoclonal antibody (“mAb”) or the antigen-binding fragment of a mAb against human vascular endothclial growth factor (“hVEGF”)—such as, e.g., a fully human-glycosylated (HuGly) anti-hVEGF antigen-binding fragment-to the retina/vitreal humour in the eye(s) of human subjects diagnosed with ocular diseases caused by increased neovascularization, for example, neovascular age-related macular degeneration (“nAMD”), also known as “wet” age-related macular degeneration (“WAMD”), age-related macular degeneration (“AMD”), and diabetic retinopathy.
Type:
Application
Filed:
April 14, 2017
Publication date:
May 2, 2019
Applicant:
REGENXBIO Inc.
Inventors:
Curran Matthew SIMPSON, Stephen YOO, Karen Fran KOZARSKY, Rickey Robert REINHARDT, Laura A. CORUZZI
Abstract: 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.
Abstract: 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.
Type:
Grant
Filed:
May 15, 2014
Date of Patent:
November 28, 2017
Assignees:
Regents of the University of Minnesota, REGENXBIO Inc.
Inventors:
R. Scott McIvor, Lalitha R. Belur, Walter Low, Carolyn Fairbanks, Karen Kozarsky