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

Methods for producing engineered exosomes and other vesicle-like biological targets, including allowing a target vesicle-like structure to react and bind with immunomagnetic particles; capturing the immunomagnetic particle/vesicle complex by applying a magnetic field; further engineering the captured vesicles by surface modifying with additional active moieties or internally loading with active agents; and releasing the engineered vesicle-like structures, such as by photolytically cleaving a linkage between the particle and engineered vesicle-like structures, thereby releasing intact vesicle-like structures which can act as delivery vehicles for therapeutic treatments.

The instant application describes improved methods and compositions for the systemic delivery of therapeutic exosomes to a subject in need thereof. In certain embodiments, the current invention reduces the amount of exosomes delivered to liver, spleen and combinations thereof to allow greater distribution to other areas of the body such as, but not limited to, the brain, pancreas, lung, kidney, muscle. In certain embodiments, the methods involve the injection of one or multiple doses of non-therapeutic exosomes prior to the injection of a suitable therapeutic dose of exosomes with a therapeutic payload. Also included are methods to improve immune clearance of exosomes in subjects by inhibiting phagocytosis.

Compositions comprising a red blood cell (RBC) having non-toxically coupled thereto a nanoparticle having a low shear modulus or low Young's modulus of less than 10 MPa and containing a drug are provided. In one embodiment, the nanoparticles are optionally coated with protein. In another embodiment, the nanoparticle has no cell-specific targeting moiety or tissue-specific targeting moiety or organ-specific targeting moiety associated therewith. Methods of delivering selected drugs to target organs use these compositions both in vivo and ex vivo treatment of disease and for imaging.

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.

The present invention relates to compositions and methods that provide novel therapies in cancer. The invention includes a phagocytic cell modified with a repressor of signal regulatory protein-alpha (SIRPα) and bound to a targeting antibody to enhance phagocytic activity of the phagocytic cell toward tumor tissue. Methods of enhancing phagocytic activity and treating a tumor are also included.

The disclosure provides NIR-II imaging probes and methods of using the NIR-II imaging probes for dynamic in vivo tracking of cells, such as stem cells, or other substances. NIR-II imaging probes can include a biocompatible NIR-II dye molecule coupled to an organic, biocompatible protein carrier complex, including a carrier protein coupled to a cell-penetrating peptide.

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.

Methods for producing engineered exosomes and other vesicle-like biological targets, including allowing a target vesicle-like structure to react and bind with immunomagnetic particles; capturing the immunomagnetic particle/vesicle complex by applying a magnetic field; further engineering the captured vesicles by surface modifying with additional active moieties or internally loading with active agents; and releasing the engineered vesicle-like structures, such as by photolytically cleaving a linkage between the particle and engineered vesicle-like structures, thereby releasing intact vesicle-like structures which can act as delivery vehicles for therapeutic treatments.

Compositions of luminescence labeled activated natural killer (aNK) cells are utilized in methods of in vivo bioluminescence imaging (BLI) for assaying and identifying genetically modified NK cells capable of targeting selected anatomical locations (e.g., bone and/or brain) or targeting selected diseased cells at selected sites.