Leland Stanford Junior University

Michael Z Lin

Hokyung Chung

Crystal L Mackall

Jun Jie Chu

Robbie Majzner

Louai Labanieh

Younghee Oh

Francois St-Pierre

Conor Jacobs

Xin Zhou

Provided herein are cell surface receptors that include an extracellular binding domain, a transmembrane domain, an intracellular signaling domain, and a protease cleavage site disposed between the extracellular binding domain and the intracellular signaling domain. In certain aspects, the cell surface receptors are engineered cell surface receptors, such as chimeric antigen receptors (CARs). Also provided are cells that include such receptors (e.g., where the cells express the receptors on their surface) and pharmaceutical compositions including such cells. Nucleic acids that encode the cell surface receptors, cells including such nucleic acids, and pharmaceutical compositions including such cells, are also provided. Also provided are methods for regulating signaling of a cell surface receptor, and methods of using the cells of the present disclosure, including methods of using such cells to administer a regulatable cell-based therapy to an individual.

Regulatable cell surface receptors and related compositions and methods

Compositions and methods for targeted treatment of cancer are disclosed. In particular, the invention relates to methods of targeting anti-cancer therapy to cells exhibiting aberrant signaling associated with cancer pathogenesis by administering synthetic signaling proteins that couple detection of an oncogenic signal to release of therapeutic agents into cancerous cells.

Rewiring aberrant cancer signaling to a therapeutic effector response with a synthetic two-component system

Engineered fusion proteins comprising a self-excising degron for controlling protein production are disclosed. In particular, the inventors have constructed fusion proteins comprising a degron connected to a protein of interest through a cleavable linker comprising a hepatitis C virus (HCV) protease site. The degron can be removed from the protein of interest by a czs-encoded HCV protease such that the protein of interest can be produced with minimal structural modification. Clinically available HCV protease inhibitors can be used to block protease cleavage such that the degron is retained after inhibitor addition on subsequently synthesized protein copies. The degron when attached causes rapid degradation of the linked protein. Such fusions of a degron to a protein of interest will be especially useful when control over protein production with minimal structural modification is desired.

Degron fusion constructs and methods for controlling protein production

Engineered orange-red fluorescent proteins with enhanced fluorescent properties, obtained by mutagenesis of mNeptune2, are disclosed. In particular, the invention relates to engineered orange-red fluorescent proteins excitable with cyan light having increased emission intensity and their use in bioluminescent resonance energy transfer systems and fluorescence and bioluminescence imaging.

Cyan-excitable orange-red fluorescent proteins and bioluminescent resonance energy transfer systems

Fluorescent protein voltage sensors for measuring membrane potential and imaging high-frequency neuronal electrical activity are disclosed. In particular, the invention relates to engineered protein voltage sensors that comprise a voltage-sensing domain comprising four transmembrane domains linked to a circularly permuted fluorescent protein, which is inserted into the extracellular loop between the third (S3) and fourth (S4) transmembrane segments of the voltage-sensing domain. Such fluorescent protein voltage sensors can be used for measuring the electrical activity of neurons, including single action potentials, trains of action potentials, and subthreshold potential changes and, in particular, for imaging high-frequency neuronal electrical activity. Additionally, fluorescent protein voltage sensors can be used for a variety of other purposes, including measuring the membrane potential of any cell, including other excitable cells such as cardiac cells and endocrine cells, and for screening agents that target ion channels for their effects on membrane potential.

Fluorescent protein voltage sensors for measuring membrane potential and imaging high-frequency neuronal electrical activity

Engineered fusion proteins comprising photochromic protein domains are disclosed. In particular, the inventors have constructed fusion proteins containing photoswitchable photochromic fluorescent protein domains linked to selected proteins and shown that such fusion proteins can be used to control the activity or localization of selected proteins with light.

Growing community of inventors

Stanford, CA, United States of America

Michael Z Lin