Adverum Biotechnologies, Inc.

Leland Stanford Junior University

University of Washington

Avalanche Australia Pty Ltd.

Exhaura, Ltd.

Thomas W Chalberg, Jr

Jay Neitz

Maureen Neitz

Daniel V Palanker

Alexander B Vankov

Philip Huie, Jr

Ian J Constable

Mehdi Gasmi

Annahita Keravala

Christopher Chavez

P Elizabeth Rakoczy

Chooi-May Lai

Mark S Blumenkranz

Michele P Calos

Michael F Marmor

Elizabeth P Rakoczy

The present disclosure provides polynucleotide cassettes, expression vectors and methods for the expression of a gene in cone cells.

Compositions and methods for enhanced gene expression in cone cells

The disclosure provides compositions and methods useful for treating conditions related to Dual Leucine Zipper (DLK), e.g., neurodegenerative disorders including optic neuropathy. The disclosure provides gene constructs and vectors that regulate the activity of Dual Leucine Zipper Kinase (DLK) or Leucine Zipper Kinase (LZK). The disclosure also provides dominant negative DLK (DN-DLK) proteins that inhibit the kinase and/or signaling activity of DLK. The disclosure also provides vectors, pharmaceutical compositions, and methods of inhibiting DLK.

Dual leucine zipper kinase inhibitors for gene therapy

Provided are mutant viral capsid cell libraries, individual cells of such libraries, systems, vectors, and methods for generating the cell libraries, and methods of use thereof to screen for mutant viral capsids with desired characteristics.

Mutant viral capsid libraries and related systems and methods

Methods and compositions are provided for intravitreally delivering a polynucleotide to cone photoreceptors. Aspects of the methods include injecting a recombinant adeno-associated virus comprising a polynucleotide of interest into the vitreous of the eye. These methods and compositions find particular use in treating ocular disorders associated with cone dysfunction and/or death.

Compositions and methods for intravitreal delivery of polynucleotides to retinal cones

The present disclosure provides compositions and methods for the prevention or treatment of ocular neovascularization, such as AMD, in a human subject, by administering subretinally a pharmaceutical composition comprising a pharmaceutically effective amount of a vector comprising a nucleic acid encoding soluble Fms-related tyrosine kinase-1 (sFlt-1) protein to the human subject.

Treatment of ocular neovascularization using anti-VEGF proteins

The present invention provides a method and apparatus for transferring an agent into a cell. The method includes the steps of providing an agent outside of a cell and generating a vapor bubble and a plasma discharge between an avalanche electrode and a conductive fluid surrounding the cell. The vapor bubble and plasma discharge generate a mechanical stress wave and an electric field, respectively. The combination of this mechanical stress wave and electric field results in permeabilization of the cell, which in turn results in transfer of the agent into the cell.

Method and apparatus for avalanche-mediated transfer of agents into cells

The present invention provides a method of treating an ocular disease in a subject. In a first step, a nucleic acid is introduced into cells or a tissue. The nucleic acid is introduced by electron avalanche transfection. With this technique, a high electric field induces a vapor bubble and plasma discharge between an electrode and the surrounding medium. The formation of a vapor bubble generates mechanical stress. Plasma discharge through the ionized vapor in the bubble enables connectivity between the electrode and the surrounding medium, so that mechanical stress and electric field are applied simultaneously, which results in permeabilization of the cells or tissue. This permeabilization in turn allows the nucleic acid to enter the cell or tissue. Cells or tissue containing the nucleic acid are then transplanted into an ocular region of the subject.

Ocular gene therapy using avalanche-mediated transfection

Growing community of inventors

Redwood City, CA, United States of America

Thomas W Chalberg, Jr