University of California

Aurora Biosciences Corporation

Aurora Discovery, Incorporated

Life Technologies Corporation

University of Oregon

Other

Massachusetts Institute of Technology

Centre National De La Recherche Scientifique

State of Oregon

Invitrogen Corporation

Vertex Pharmaceuticals (san Diego) LLC

Nexus Biosystems, Inc.

Roger Y Tsien

Alec Tate Harootunian

Roger Heim

Andrew A Pham

Peter J Coassin

Andrew B Cubitt

Tao Jiang

Gregor Zlokarnik

Jesus E Gonzalez, Iii

Quyen T Nguyen

Stephen R Adams

S James Remington

B Albert Griffin

Tom Knapp

Emilia S Olson

Paul Negulescu

Atsushi Miyawaki

Harry Stylli

Geoffrey S Baird

Michael A Whitney

Robert E Campbell

Minh Vuong

Peter N Pham

Juan Llopis

Akwasi Minta

Mike Whitney

Tim Rink

Elamprakash N Savariar

Mats F Ormo

Gregory Zlokarnik

Dina Hingorani

Timothy Rink

Lei Wang

Jianghong Rao

Jin Z Zhang

Robert Earl Campbell

Carsten Schultz

Evan Walker Miller

Rebekka M Wachter

Xiaokun Shu

Grzegorz Grynkiewicz

Nathan C Shaner

Wenhong Li

Christina Hauser

Mats F Orm&ouml;

Todd Aguilera

John D Mendlein

Stephen J Lippard

Chari Stylli

Susan S Taylor

Jessica Crisp

Scott Hilderbrand

Paul A Negulescu

Ying Ji

Sunil J Advani

Eric T Ahrens

Richard Ting

Shawn Burdette

Alexandra C Newton

Antoine Royant

William E Moerner

Lewis R Makings

Robert M Dickson

Peter J Cassin

Erik Rodriguez

Michael Z Lin

John Lin

Geraldine Tran

Paul Steinbach

Mats F Ormö

Grant K Walkup

David A Zacharias

Alice Y Ting

Alexander A Kislukhin

John Yu-luen Lin

Toshiaki Furuta

Jonathan D Violin

The present invention provides methods for guiding preservation of human neurons or human nerves during surgery by administering a fluorescently-labeled peptide that specifically binds to the human neurons or human nerves. The invention further provides human neuron or nerve targeting molecules comprising fluorescently-labeled peptides that specifically bind to human neurons or human nerves and compositions thereof.

Optimized peptides for targeting human nerves and their use in image guided surgery, diagnostic and therapeutic delivery

This disclosure provides compositions of metal-binding fluorinated compounds and associated methods for producing cellular labels for tracking cells by magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and related methods.

Compositions and methods for imaging cell populations

Optimized peptides for targeting human nerves and their use in image guided surgery, diagnostics and therapeutic

Disclosed herein, in certain embodiments, is a selective transport molecule with increased in vivo circulation. In some embodiments, a selective transport molecule disclosed herein has the formula (A-X-B-C)-M, wherein C is a cargo moiety; A is a peptide with a sequence comprising 5 to 9 consecutive acidic amino acids, wherein the amino acids are selected from: aspartates and glutamates; B is a peptide with a sequence comprising 5 to 20 consecutive basic amino acids; X is a linker; and M is a macromolecular carrier.

Peptides whose uptake in cells is controllable

Compounds and methods for determining transmembrane potential, monitoring changes in transmembrane potential, and/or drug screening are provided. In one aspect, compounds of the invention have a structure according to the formula: E-M-A, wherein A is a fluorophore, selected from xanthenes, coumarins, cyanines, bimanes, and difuloroboradizaindacenes, charged at physiological pH; M is a molecular wire; and E is a hydrophobic moiety, wherein A and E are capable of being involved in a photo-induced, intramolecular electron transfer that quenches the fluorescence of A in response to a voltage condition. When in use, compounds of the invention are membrane-impermeant and oriented within the cell membrane such that the charged moiety localizes at the outer leaflet of the lipid bilayer and the hydrophobic moiety and molecular wire associate with the hydrophobic portion of the lipid bilayer. The rate of electron transfer, fluorescence intensity, and quenching are altered in response to changes in transmembrane potential.

Fluorescent probes for monitoring voltage by photo-induced electron transfer

Optimized peptides for targeting human nerves and their use in image guided surgery, diagnostics and therapeutic delivery

Disclosed herein, the invention pertains to methods and compositions that find use in radiosensitization of tumors and tumor samples based on the ability of a tumor sample to cleave a MTS molecule of the present invention. The MTS molecules of the present invention have a formula as disclosed herein and wherein A is a peptide with a sequence comprising 5 to 9 consecutive acidic amino acids, wherein the amino acids are selected from: aspartates and glutamates; B is a peptide with a sequence comprising 5 to 20 consecutive basic amino acids; X and Y are linkers; P is an optional pre-targeting moiety; M is an optional macromolecular carrier; and T is a radiosensitization agent for delivery to a target, including for example a therapeutic compound.

Tumor radiosensitization with monomethyl auristatin E (MMAE) and derivatives thereof

The invention provides evolved red-shifted smURFPs. In some embodiments, the smURFPs are characterized by a) increased Fluorescence of smURFP as compared to infrared FPs IFP1.4 and iRFP713; b) expressing efficiently with minimal toxicity; c) does not require a lyase to covalently attach its chromophore, wherein the chromophore is biliverdin; d) exhibit a wavelengths longer than attainable with jellyfish- or coral-derived FPs using smURFP and IFP2.0; e) allows for functional fusion to hCdt1(30/120) as compared to jellyfish- or coral-derived FPs mAG, eGFP, and mRFP1 which are nonfunctional; and f) allows for deep tissue imaging.

Allophycocyanin alpha-subunit evolved labeling proteins (smURFPs)

Disclosed herein, the invention pertains to methods and compositions that find use in diagnostic, prognostic and characterization of neoplasia samples based on the ability of a neoplasia sample to cleave a MTS molecule of the present invention. In some embodiments, a MTS molecule disclosed herein has the formula (A-X-B-C), wherein A is a peptide with a sequence comprising 5 to 9 consecutive acidic amino acids, wherein the amino acids are selected from: aspartates and glutamates; B is a peptide with a sequence comprising 5 to 20 consecutive basic amino acids; X is a linker; and C is a detectable moiety.

Personalized protease assay to measure protease activity in neoplasms

A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. X may be cleaved extracellularly or intracellularly. The molecules of the present invention may be linear, cyclic, branched, or have a mixed structure.

Peptides whose uptake by cells is controllable

Imaging systems for fluorescence guided surgery are provided. An imaging system comprises a light source unit for providing one or more illumination and excitation lights to a target, a detection unit for detecting reflectance and fluorescence from the target, an optical train for directing the one or more illumination and excitation lights from the light source unit to the target and for directing the reflectance and fluorescence from the target to the detection unit, and a control unit for controlling the light source unit and the detection unit. Imaging methods for fluorescence guided surgery are also provided.

Imaging system and method for fluorescence guided surgery

Disclosed herein, the invention pertains to methods and compositions that find use in treatment, diagnosis, prognosis and characterization of disease and disease samples based on the ability of a disease sample to cleave a MTS molecule of the present invention. The MTS molecules of the present invention have a formula as disclosed herein and wherein A is a peptide with a sequence comprising 5 to 9 consecutive acidic amino acids, wherein the amino acids are selected from: aspartates and glutamates; B is a peptide with a sequence comprising 5 to 20 consecutive basic amino acids; X and Y are linkers; P is a pre-targeting moiety; M is a macromolecular carrier, C is a detectable moiety; and T is a compound for delivery to a target, including for example a therapeutic compound.

Pretargeted activatable cell penetrating peptide with intracellularly releasable prodrug

Disclosed herein, in certain embodiments, is a selective transport molecule with increased in vivo circulation. In some embodiments, a selective transport molecule disclosed herein has the formula (A-X-B-C)n-M, wherein C is a cargo moiety; A is a peptide with a sequence comprising 5 to 9 consecutive acidic amino acids, wherein the amino acids are selected from: aspartates and glutatmates; B is a peptide with a sequence comprising 5 to 20 consecutive basic amino acids; X is a linker; and M is a macromolecular carrier.

The invention provides compositions useful as molecular probes. In particular, the invention provides activatable cell penetrating peptides comprising a fluorescence donor and a fluorescence acceptor. Exemplary fluorescence donors and fluorescence acceptors include compounds derived from cyanine. Also provided are ratiometric, multispectral, and excitation lifetime imaging methods for detecting the molecular probes provided herein.

Activatable cell penetrating peptides with quenched fluorophores

Growing community of inventors

La Jolla, CA, United States of America

Roger Y Tsien