University of Iowa Research Foundation

Massachusetts Institute of Technology

The Broad Institute, Inc.

The Children's Hospital of Philadelphia

Editas Medicine, Inc.

Other

National Institutes of Health, a Component of the US Dept. of Health & Human Services

Chiron Corporation

The General Hospital Corporation

Fondazione Telethon

Chen, Yong Hong

Davidson, Beverly L.

Beverly L Davidson

Ryan Boudreau

Paul B McCray, Jr

Alejandro Mas Monteys

Scott Harper

Edgardo Rodriguez

Feng Zhang

Henry Paulson

Colleen Stein

Haibin Xia

Jordi Mata-Fink

Yong Hong Chen

Alexis Borisy

Deborah Palestrant

Jodi McBride

Qinwen Mao

Douglas J Jolly

Victor Miller

Cynthia Gouvion

Mark Aaron Behlke

Thomas W Dubensky, Jr

John A Chiorini

Robert Michael Kotin

Chie-yu Lin

Patrick Sinn

Sybille L Sauter

Hong Peng Jia

Anthony J Fischer

Maureen D Donovan

Lane K Law

Jason A Heth

Sateesh Krishnamurthy

Kevin P Campbell

Gordon L Amidon

Michael A Apicella

David Wiemer

John R Crison

Alberto Auricchio

Mordechai Bodner

Roger Williamson

Bradley T Hyman

Franck Duclos

Joseph Zabner

Volker Straub

Chie-Yu Lin

John H Lee

Leland E Lim

Richard D Anderson

Yonghong Chen

Megan S Keiser

Guoshun Wang

Steven M Herrmann

Shauna Ebanks

Carolyn M Yrigollen

Bryan Simpson

Ronald Haskell

Luis Tecedor

Maria Scheel

Kathleen H Holt

Aliye Uc

John M Hilfinger

Abhay Divekar

Steven J Beer

Ryan L Boudreau

Eloise Hudry

Jodi L Mcbride

Alejandro Monteys

The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences especially for use as to nucleotide repeat disorders. Provided are delivery systems and tissues or organ which are targeted as sites for delivery especially for use as to nucleotide repeat disorders. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex or system especially for use as to nucleotide repeat disorders, as well as methods for the design and of such. Also provided are methods of directing CRISPR complex or system formation in eukaryotic cells especially for use as to nucleotide repeat disorders including with consideration of specificity for target recognition and avoidance of toxicity and editing or modifying a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Compositions and methods of use of CRISPR-Cas systems in nucleotide repeat disorders

The invention relates to sulfamidase (SGSH) and SGSH variants. SGSH and SGSH variants can be delivered by way of a recombinant adeno-associated virus (rAAV) particle to a mammal's central nervous system (CNS) to transduce CNS cells that contact cerebrospinal fluid (CSF). Target mammals for SGSH and SGSH variant administration include mammals with a deficiency or defect in SGSH expression or function.

Sulfamidase (SGSH) variants, vectors, compositions and methods and uses for treating mucopolysaccharidosis type IIIA (MPS IIIA)

The present disclosure provides methods for treating or preventing Huntington's disease (HD) in a subject in need thereof, comprising administering a therapeutic agent that activates mTORC 1 function and/or increases Ras Homolog Enriched in Striatum (Rhes) level in the subject's brain as compared to the function or level in the subject prior to treatment, and methods for modulating mHTT-associated metabolic phenotypes and/or reversal of striatal atrophy by administering a therapeutic agent that activates mTORC1 function and/or increases Ras Homolog Enriched in Striatum (Rhes) level in the subject's brain as compared to the function or level in the subject prior to treatment.

Method for treating Huntingtons's disease

The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a SIN CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing SIN CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Compositions and methods are provided for the inhibition, treatment and/or prevention of fragile X syndrome and related disorders.

Compositions and methods for treating fragile X syndrome and related syndromes

Compositions and methods are provided for the inhibition, treatment and/or prevention of Huntington's disease and related disorders.

Compositions and methods for treating Huntington's disease and related disorders

Disclosed herein are methods and compositions useful in targeting a payload to, or editing a target nucleic acid, where a governing gRNA molecule is used to target, optionally inactivate, a Cas9 molecule or a Cas9 molecule/gRNA complex.

CRISPR-related methods and compositions with governing gRNAS

The present disclosure provides filler or stuffer sequences, compositions thereof including expression cassettes and vectors, such as viral (e.g., AAV) vectors and methods of delivering a therapeutic agent to a mammal and/or treating a disease.

Therapeutic for treatment of diseases including the central nervous system

The present disclosure provides methods of treating a disease or delivering a therapeutic agent to a mammal comprising administering to the mammal's deep cerebella nuclei a recombinant adeno-associated virus (rAAV) particle comprising an AAV capsid protein and a vector comprising a nucleic acid encoding a therapeutic agent inserted between a pair of AAV inverted terminal repeats in a manner effective to infect the CNS cell of the non-rodent mammal such that the CNS cell expresses the therapeutic agent in the non-rodent mammal.

Methods of delivery of transgenes for treating brain diseases

CRISPR-related methods and compositions with governing gRNAs

The present disclosure provides targeting peptides and vectors containing a sequence that encodes targetting peptides that deliver agents, to the eye. The present inventors have discovered peptides that function to target agents, such as viral vectors, to ocular cells. The present disclosure describes a method to utilize these novel peptides to direct, for example, viral capsids to the cell type of interest. In this instance, ocular cells (such as retinal cells) are targeted by the identified peptides. Vectors harboring capsid proteins modified to include such peptides can be used to provide therapeutic agents to the eye.

Methods and compositions for treating genetic eye diseases

The present disclosure provides methods of treating a disease or delivering a therapeutic agent to a mammal comprising administering to the mammal's cisterna magna and/or ventricle an rAAV particle containing a vector comprising a nucleic acid encoding a therapeutic protein inserted between a pair of AAV inverted terminal repeats in a manner such that cells with access to the cerebrospinal fluid (CSF) express the therapeutic agent and in certain embodiments secretes the therapeutic agent into the CSF for distribution to the brain.

Methods and compositions for treating brain diseases

An isolated promoter sequence comprising a nucleic acid of between 600 and 1700 nucleotides in length having at least 90% identity to SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7.

Promoter compositions

Growing community of inventors

North Liberty, IA, United States of America

Beverly L Davidson