University of California

University of Pennsylvania

Howard Hughes Medical Institute

Integrative Gene Therapeutics

David V Schaffer

John G Flannery

James T Koerber

Leah Caroline Thomas Byrne

Meike Visel

Ryan R Klimczak

Kevin Edward Healy

Deniz Dalkara Mourot

Brian K Kaspar

Samuel Thomas Wall

Narendra Maheshri

Bum-Yeol Hwang

Krishanu Saha

William Beltran

Irina M Conboy

Hanadie Yousef

Michael J Conboy

Patrick Sean Daugherty

Loren Lee Looger

Wesley M Jackson

Joshua Dudman

Dougal Gowanlock Robinson Tervo

Alla Karpova

Eda Isil Altiok

Adam Hantman

Lauren Little

Kimberly Ritola

Joshua N Leonard

Sarada Viswanathan

David Stephen Ojala

Melissa A Kotterman

Rachel A Segalman

Philip A Romero

Benjamin Ezra Epstein

Oscar Westesson

Timothy P Day

Leah C Byrne

Wendy Cousin

Christian Elabd

Julie H Yu

Nicole Anne Repina

Ruoxing Lei

Thomas Patrick C McClave

Jorge Santiago-Ortiz

Gonçalo Rodrigues

Ian H Holmes

Christina Marie Fuentes

John Weinstein

Barbara L Ekerdt

Yuguo Lei

Leah Ct Byrne

Kevin E Healy

Samuel T Wall

Leah CT Byrne

David S Ojala

The present disclosure provides recombinant adeno-associated virus (AAV) virions with altered capsid protein, where the recombinant AAV (rAAV) virions exhibit greater ability to cross barriers between intravitreal fluid and retinal cells, and thus greater infectivity of a retinal cell compared to wild-type AAV, and where the rAAV virions comprise a heterologous nucleic acid. The present disclosure provides methods of delivering a gene product to a retinal cell in an individual.

Compositions and methods of treating ocular diseases

Provided are systems and methods for spatially and temporally controlling light with an illumination device comprising a light source operably connected to a circuit board, one or more light guide plates, one or more optical masks, a controller, and a computer readable medium, comprising instructions that, when executed by the controller, cause the controller to: illuminate a cell or a substrate with light from the light source, and spatially and temporally control illumination of light to the cell or the substrate with one or more illumination parameters, wherein the one or more light guide plates provides uniform illumination of the light. Also provided herein are methods of screening using the system and/or device of the present disclosure.

Illumination device for spatial and temporal control of morphogen signaling in cell cultures

The present disclosure provides AAV variants that exhibit a preference for retrograde movement in neurons and methods of using such variants.

Variant adeno-associated viruses and methods of using

The present disclosure provides methods of treating an ocular disease or disorder. The methods involve direct administration into the eye of a conjugate comprising a biologically active polypeptide and a biocompatible polymer.

Methods of treating an ocular disease or disorder

The present disclosure provides recombinant adeno-associated virus virions with variant capsid protein, where the recombinant AAV (rAAV) virions exhibit one or more of increased ability to cross neuronal cell barriers, increased infectivity of a neural stem cell, increased infectivity of a neuronal cell, and reduced susceptibility to antibody neutralization, compared to a control AAV, and where the rAAV virions comprise a heterologous nucleic acid. The present disclosure provides methods of delivering a gene product to a neural stem cell or a neuronal cell in an individual. The present disclosure also provides methods of modifying a target nucleic acid present in a neural stem cell or neuronal cell.

Adeno-associated virus capsid variants and methods of use thereof

The present disclosure provides infectious recombinant adeno-associated virus (rAAV) virions that comprise a variant capsid protein and a heterologous nucleic acid. The present disclosure further provides the variant adeno-associated virus (AAV) capsid proteins (and/or a nucleic acid encoding the variant AAV capsid proteins), which confer to an infectious rAAV virion an increased resistance to human AAV neutralizing antibodies. The present disclosure further provides host cells comprising an infectious rAAV virion and/or a nucleic acid encoding a subject variant AAV capsid protein. The present disclosure further provides methods of delivering a heterologous nucleic acid to a target cell where the target cell is contacted with a subject infectious rAAV virion. The present disclosure further provides methods of delivering a gene product to an individual, the methods generally involving administering an effective amount of a subject rAAV virion to an individual in need thereof.

Compositions and methods of treatment

The present disclosure provides adeno-associated virus (AAV) virions with altered capsid protein, where the AAV virions exhibit greater infectivity of retinal cells compared to wild-type AAV. The present disclosure further provides methods of delivering a gene product to a retinal cell in an individual, and methods of treating ocular disease.

Adeno-associated virus virions with variant capsid and methods of use thereof

Disclosed herein is a functional nucleic acid that includes i) one or more coding nucleotide sequences encoding a genome editing endonuclease; ii) regulatory sequences operably linked to the one or more coding nucleotide sequences; and iii) one or more genome editing endonuclease-recognized sequences, wherein the functional nucleic acid is configured to express the endonuclease in a host cell and thereby provide a cellular endonuclease activity in a sequence-specific manner in the host cell, and wherein cleavage of the functional nucleic acid by the endonuclease inactivates the cellular endonuclease activity. Methods of using the present functional nucleic acid, and systems and kits that find use in performing the same are also provided.

Self-inactivating endonuclease-encoding nucleic acids and methods of using the same

The present invention provides polypeptide-polymer conjugates. A subject polypeptide-polymer conjugate is useful in a variety of applications, which are also provided.

Polypeptide-polymer conjugates and methods of use thereof

The present disclosure provides adeno-associated virus (AAV) virions with altered capsid protein, where the AAV virions exhibit greater infectivity of retinal cells, when administered via intravitreal injection, compared to wild-type AAV. The present disclosure further provides methods of delivering a gene product to a retinal cell in an individual, and methods of treating ocular disease.

Adeno-associated virus virions with variant capsid

Adeno-associated virus variants and methods of use thereof

The present disclosure provides a three-dimensional culture system comprising a biocompatible polymer and a combination of factors in an amount effective to induce differentiation of oligodendrocyte precursors and/or oligodendrocytes from pluripotent stem cells. The present disclosure provides methods of generating oligodendrocyte precursors and/or oligodendrocytes using a three-dimensional culture system of the present disclosure. The present disclosure provides methods to treat neurological diseases and demyelinating diseases.

Compositions and methods for generating oligodendrocyte precursors

The present disclosure provides thermoreversible polymers, hydrogel compositions comprising the thermoreversible polymers, as well as methods of making and using the thermoreversible polymers.

Thermoreversible polymers and methods of use thereof

Growing community of inventors

Danville, CA, United States of America

David V Schaffer