Sequences that enhance permeation of agents into cells and/or across the blood brain barrier, compositions comprising the sequences, and methods of use thereof.

A bifunctional linker of Formula 1

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wherein in Formula I, at least one of R.sup.1 to R.sup.4 is —COOR.sup.5 and R.sup.5 is —C.sub.0-C.sub.10alkyl(C.sub.2-C.sub.10alkynyl) or —C.sub.0-C.sub.10alkyl-C.sub.2-C.sub.10alkenyl(C.sub.2-C.sub.10alkynyl), preferably a terminal alkynyl. The bifunctional linker is used in a cycloaddition to tether two entities, for example a protein or antibody, and an active agent, to form a bisconjugate. The bifunctional linker also be used to form a conjugate, followed by cycloaddition in the presence of a comonomer composition to form a bisconjugate including a protein or antibody linked to an adhesive polymer network. Catalysis can be provided by a copper-containing paint on a surface to adhere the bisconjugate to the surface. Methods of synthesis and use of the bisconjugates imaging, diagnostic, and therapeutic applications are also described.

Closed cavity adjustable sensor mount systems include a sealed, closed cavity enclosing a sensor and forming a closed cavity sensor assembly. The closed cavity sensor assembly may be tilted and/or translated relative to a platform in order to adjust the orientation of the sensor to align it with an imaging optical axis. Following alignment, the closed cavity sensor assembly may be permanently or reversibly fixed in place. The closed cavity adjustable sensor mount systems may be part of medical imaging systems such as endoscopic imaging systems and/or open field imaging systems.

Calcium reacting photoproteins are a class of self-illuminating proteins that emit light upon contact with calcium. Fluorescent Proteins are small proteins that change the color of light when excited. Fluorescent Proteins and Calcium Activated Photoproteins can be used to enhance, dazzle, amaze, startle, and otherwise entertain an audience by their direct application on to the audience, surroundings, the actors, or sprayed on settings as in the newer 4D movies. The disclosure comprises novel Coelenterazine compounds and methods of use, including a simple delivery device for the photoprotein to create unique and novel cinematic, theatrical, stage, movie and musical concert optical effects by their luminous reaction upon contact with surfaces that contain calcium. Calcium is ubiquitous in and on most surfaces and in the environment; it is this unique property of calcium that makes this a novel use of the photoproteins for entertainment.

The present invention is based on the development of artificial targeting sequences that enhance permeation of agents into cells and across the blood brain barrier, compositions comprising the sequences, and methods of use thereof. Provided herein is an AAV comprising a capsid protein comprising a targeting sequence and a transgene, preferably a therapeutic or diagnostic transgene. Further, provided herein are methods of delivering a transgene to a cell, the method comprising contacting the cell with an AAV or fusion protein described herein.

Novel compounds in the classes of Imidazo[1,2-α]pyrazines and Imidazo[1,2-α]quinoxalines with a methoxy group modification show unique spectral properties when used as a substrate for luciferases and photo-proteins. Methoxy e-Coelenterazine, an Imidazo[1,2-α] quinoxaline shifts the emission wavelength by 80 nm to blue light compared to e-Coelenterazine, using Renilla reniformis luciferase. The novel analogues described here are useful in combination with fluorescent proteins to create BRET (bioluminescent resonance energy transfer) and for other luminescent assays. In addition these novel compounds can be used to enhance, dazzle, amaze, startle, and otherwise entertain an audience by their direct application on to the audience, surroundings, the actors, or sprayed on settings as in the newer 4D movies.

A method for conjugating an isolated antibody to a label or derivatisation reagent, which method comprises contacting the antibody with an activated label or activated derivatisation reagent, or contacting the antibody with the label or derivatisation reagent in the presence of an antibody conjugation reagent, in a buffer system which comprises a monocarboxylic acid buffer compound other than glycine, bearing an amine substituent at the alpha or beta position.

Provided herein are devices and methods used to produce tattoo biosensors that are based on spatially controlled intracutaneous gene delivery of optical reporters driven by specific transcription factor pathways for a given cytokine or other analyte. The biosensors can be specific to a given analyte, or more generically represent the convergence of several cytokines into commonly shared intracellular transcription factor pathways. These biosensors can be delivered as an array in order to monitor multiple cytokines. Biosensor redeployment can enable chronic monitoring from months to years. The tattooed biosensor array of the present invention includes endogenous reporter cells, naturally tuned to each patient's own biology and can be used to reliably measure the state of a patient in real-time.

This invention provides the nucleic acid molecules encoding novel small monomeric near-infrared fluorescent protein miRFP670nano, variants and derivatives thereof as well as proteins and peptides encoded by these nucleic acids. The invention also relates to derivatives, homologues, or mutants of the specific proteins referenced above as well as fragments of the nucleic acids and the peptides encoded thereby. The invention further relates to host-cells, stable cell lines and transgenic organisms comprising above-referenced nucleic acid molecules. The present invention also refers to methods of making and using small monomeric near-infrared fluorescent proteins derived from cyanobacteriochromes. The presented protein and its derivatives find use in a variety of applications and approaches, including labeling of biomolecules, cells or cell organelles, detecting protein-protein interactions, and generation of genetically encoded fluorescent biosensors.

The present invention provides a protein fusion construct comprising a far-red cyanobacteriochrome (CBCR) domain linked to a heterologous domain, wherein the far-red CBCR domain comprises a CBCR polypeptide and a tetrapyrrole chromophore. The invention also provides nucleic acids, expression cassettes, vectors, and host cells for expression of the far-red CBCR protein fusion constructs. Methods for detecting cellular components, methods for imaging biological structures, and method for modulating cellular processes using the protein fusion constructs are also provided.