Wisconsin Alumni Research Foundation

Emory University

Cedars-sinai Medical Center

Eric V Shusta

Sean Paul Palecek

Yongku Peter Cho

Clive N Svendsen

Brantley R Herrin

Ethan S Lippmann

Samira M Azarin

Tongcheng Qian

Charles C Stutz

Xin Xiang Wang

Paul A Clark

Benjamin J Umlauf

Gad Vatine

Carrie J Marshall

Jason M Lajoie

John Kuo

Scott G Canfield

Michael Zorniak

John Shu-Shin Kuo

Matthew Stebbins

Benjamin J Tillotson

Alane E Wentz

Christian Weidenfeller

Tej Pavoor

Angela R Jones

Gad D Vatine

Samira Azarin

The present disclosure provides isolated polypeptides comprising variable lymphocyte receptors that specifically bind the blood brain barrier, compositions, and methods of use.

Variable lymphocyte receptors that target the blood brain barrier and methods of use

The present invention provides antibodies or antigen binding fragments thereof including single chain variable fragment (scFv) antibodies that specifically bind to the blood brain barrier in vivo and methods of use.

Blood brain barrier (BBB)-selective antibodies and methods of use thereof to target agents to the BBB

The present disclosure provides isolated polypeptides comprising variable lymphocyte receptors that specifically bind the brain extracellular matrix, compositions, and methods of use. Methods of using the variable lymphocyte receptors for the detection and treatment of disease or injury, specifically, for example, cancers including glioblastoma are provided.

Variable lymphocyte receptors that target the brain extracellular matrix and methods of use

The present invention provides methods and kits for differentiating podocytes from pluripotent stem cells and from other cell types.

Method of differentiating human pluripotent stem cells to podocytes

A method of creating an isogenic multicellular blood-brain barrier model from iPSCs is disclosed.

Isogenic blood-brain barrier model

The present invention provides antibodies that target glioblastoma stem-like cells and methods and kits for their use.

Antibodies targeting glioblastoma stem-like cells and methods of use thereof

A population of brain pericyte-like cells, wherein the cells express pericyte markers but do not express ACTA2 and wherein the cells are generated from hPSCs, is disclosed herein.

Method of creating human pluripotent stem cell derived brain pericyte-like cells

In one embodiment, the present invention is a method of creating a fully-human blood-brain barrier (BBB) model, comprising the steps of (a) obtaining a mixture of neural cells and brain microvascular endothelial cells (BMECs), wherein the neural cells and BMECs that comprise the mixture were produced from the differentiation of human pluripotent stem cells (hPSCs); (b) purifying BMECs from the mixture of neural cells and BMECs of step (a); and (c) co-culturing the purified BMECs with a cell type selected from the group consisting of pericytes, astrocytes and differentiated neural progenitor cells (NPCs), wherein a blood brain barrier model is created.

Retinoic acid enhanced human stem cell derived blood brain barrier model

A pH-dependent antibody that binds an antigen with high affinity at a first pH and rapidly dissociates at a second pH, wherein the antigen is a transferrin receptor (TfR), wherein the association at the second pH/the first pH is less than 20%, and wherein the pH-dependent antibody comprises at least two consecutive histidine residues at a single complementarity determining region (CDR) is disclosed.

pH-dependent antibodies targeting the transferrin receptor and methods of use thereof to deliver a therapeutic agent

Methods for generating functional brain microvascular endothelial cells (BMECs) under chemically defined, serum-free conditions are provided. In particular, efficient and cost-effective methods for generating functional BMECs under chemically defined culture conditions are provided. BMECs obtained according to the methods provided herein are suitable for in vitro blood brain barrier (BBB) formation.

Methods for differentiation of human pluripotent stem cells to brain microvascular endothelial cells

A model blood brain barrier obtained from hPSCs is disclosed.

Human blood-brain barrier endothelial cells derived from pluripotent stem cells and blood-brain barrier model thereof

The invention discloses engineered non-self-cleaving inteins derived from Mxe GyrA inteins and methods of using such inteins to chemically modify proteins.

Engineered intein for improved production of protein-intein fusions

This application discloses a BBB-selective antibody. The BBB-selective antibody comprises a protein encoded by a DNA sequence comprising SEQ ID NO:7 (CDRH1 of scFv 15), SEQ ID NO:8 (CDRH2 of scFv 15), SEQ ID NO:9 (CDRH3 of scFv 15), SEQ ID NO:10 (CDRL1 of scFv 15), SEQ ID NO:11 (CDRL2 of scFv 15) and SEQ ID NO:12 (CDRL3 of scFv 15) or a DNA sequence comprising SEQ ID NO:19 (CDRH1 of scFv 38), SEQ ID NO:20 (CDRH2 of scFv 38), SEQ ID NO:21 (CDRH3 of scFv 38), SEQ ID NO:22 (CDRL1 of scFv 38), SEQ ID NO:23 (CDRL2 of scFv 38) and SEQ ID NO:24 (CDRL3 of scFv 38). Preferably, the BBB-selective antibody comprises a protein encoded by SEQ ID NO:1 or 3.

Blood-brain barrier targeting antibodies

A family of GFP scaffolds capable of accommodating two proximal, randomized binding loops is disclosed. GFP-based binders binding with nanomolar affinity are developed from a library of these GFP scaffolds.

GFAbs: GFP-based biosensors possessing the binding properties of antibodies

A method of creating a multicellular blood-brain barrier model is disclosed. In one embodiment, the method comprises culturing primary brain microvascular endothelial cells or embryonic stem cell-derived endothelial cells upon a permeable support in the presence of neural progenitor cells.

Growing community of inventors

Madison, WI, United States of America

Eric V Shusta