Abstract: The present invention features assays for co-culturing primary cells while maintaining key biological activities specific to the primary cells. The invention is based, at least in part, on the discovery that compositions and methods for primary cells in a high-throughput co-culture platform, image analysis for distinguishing cells in co-cultures and assays that are suitable for screening of agents in epithelial cells, such as hepatocytes.

Abstract: A nanoparticle activity sensor containing a reporter and at least one tuning domain that modifies a distribution or residence time of the activity sensor when administered to a patient. When administered to the patient, the activity sensor enters cells or tissue where it is cleaved by enzymes specific to a physiological state such as a disease to release a detectable analyte. The tuning domains include molecular structures that modulate distribution or decay by protecting the particle from premature cleavage and indiscriminate hydrolysis, shielding the particle from immune detection and clearance, or by targeting the particle to specific tissue, bodily fluids, or cell types.

Abstract: The present disclosure provides patterned biomaterials having organized cords and extracellular matrix embedded in a 3D scaffold. According, the present disclosure provides compositions and applications for patterned biomaterials. Pre-patterning of these biomaterials can lead to enhanced integration of these materials into host organisms, providing a strategy for enhancing the viability of engineered tissues by promoting vascularization.

Abstract: The present invention provides methods of inducing proliferation of and/or differentiating cells comprising contacting cells with compounds within the methods of the invention. The present invention further provides cells obtainable by the methods of the invention.

Abstract: The present disclosure provides patterned biomaterials having organized cords and extracellular matrix embedded in a 3D scaffold. According, the present disclosure provides compositions and applications for patterned biomaterials. Pre-patterning of these biomaterials can lead to enhanced integration of these materials into host organisms, providing a strategy for enhancing the viability of engineered tissues by promoting vascularization.

Abstract: Some embodiments described herein relate to cells which have been genetically engineered to release a polypeptide when a population of the cells reaches a desired density. In some embodiments, the released polypeptide may be a therapeutic polypeptide. In some embodiments, the therapeutic polypeptide kills tumor cells or which inhibits the growth of tumor cells.

Abstract: Some embodiments described herein relate to cells which have been genetically engineered to release a polypeptide when a population of the cells reaches a desired density. In some embodiments, the released polypeptide may be a therapeutic polypeptide. In some embodiments, the therapeutic polypeptide kills tumor cells or which inhibits the growth of tumor cells.

Abstract: Methods and compositions for screening or diagnosis of liver disease are provided. The results may also indicate course and efficacy of treatment. The composition includes an activity sensor and a reporter releasably attached to the activity sensor. The method includes detecting the presence and/or amount of a reporter. The reporter is released from an activity sensor in the presence of diseased liver tissue but remains attached to the activity sensor in healthy tissue. The presence and/or amount of the reporter are used to characterize the liver disease. The liver disease may be nonalcoholic steatohepatitis (NASH) and results may further indicate staging of NASH.

Abstract: Some embodiments described herein relate to cells which have been genetically engineered to release a polypeptide when a population of the cells reaches a desired density. In some embodiments, the released polypeptide may be a therapeutic polypeptide. In some embodiments, the therapeutic polypeptide kills tumor cells or which inhibits the growth of tumor cells.

Abstract: Compositions useful in the controlled delivery of therapeutic agents and their methods of preparation and use are provided. The compositions comprise an optionally oxidized porous silicon core, a layer on the surface of the porous silicon core that comprises a metal silicate, and a therapeutic agent. The compositions optionally further comprise one or more targeting agents and/or cell-penetrating agents to enable the particles to target and enter cells or tissues of interest in a treated subject.

Abstract: Methods and compositions for screening or diagnosis of liver disease are provided. The results may also indicate course and efficacy of treatment. The composition includes an activity sensor and a reporter releasably attached to the activity sensor. The method includes detecting the presence and/or amount of a reporter. The reporter is released from an activity sensor in the presence of diseased liver tissue but remains attached to the activity sensor in healthy tissue. The presence and/or amount of the reporter are used to characterize the liver disease. The liver disease may be nonalcoholic steatohepatitis (NASH) and results may further indicate staging of NASH.

Abstract: The present invention features assays for co-culturing primary cells while maintaining key biological activities specific to the primary cells. The invention is based, at least in part, on the discovery that compositions and methods for primary cells in a high-throughput co-culture platform, image analysis for distinguishing cells in co-cultures and assays that are suitable for screening of agents in epithelial cells, such as hepatocytes.

Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Abstract: The present invention features assays for co-culturing primary cells while maintaining key biological activities specific to the primary cells. The invention is based, at least in part, on the discovery that compositions and methods for primary cells in a high-throughput co-culture platform, image analysis for distinguishing cells in co-cultures and assays that are suitable for screening of agents in epithelial cells, such as hepatocytes.

Abstract: Methods of the present invention predict a physiological state of a subject. A composition comprising activity sensors is introduced into a body of a subject. The activity sensors comprise a plurality of reporters susceptible to cleavage when processed by the body during extracellular matrix remodeling. Cleavage may be indicative of enzymatic activity in the extracellular matrix. Signals detected by the activity sensors may be predictive of a physiological state. A sample is collected from the subject, and liberated reporters are detected in the sample. An onset of the physiological state of the subject, which may be a disease characterized by inflammation or atrophy, may be diagnosed based on the liberated reporters detected.

Abstract: The present invention provides method for longitudinal monitoring of disease changes and/or drug response. At multiple time points, a composition is introduced into a body of a subject (the composition includes an activity sensor comprising a plurality of reporters liberated through enzymatic cleavage, which occurs in a tissue of the body when enzymes associated with known activity of a therapeutic intervention are present in the body) and reporters are detected to determine activity levels of disease-associated enzymes in the subject, which is correlated to changes in disease state and/or drug response. A report or therapeutic response profile may further be used to support a clinical trial and for longitudinal monitoring of disease progression or regression in a subject. A prospective or active clinical trial participant, or patient undergoing treatment, may be qualified, stratified or staged based on the determined activity levels.

Abstract: The invention provides methods and compositions that use a process in the body to deliver an active form of the activity sensor to a target site within the body. The activity sensors, which release detectable reporters when acted on by certain enzymes within the body, are provided as pro-analytes. Processes within the body deliver the activity sensors in active form to a target site of interest. For example, enzymes or a chemical environment within the body may cleave blocking groups from the activity sensors, or the body's tissues and organs may collect the activity sensors at the target site based on size or composition of the activity sensors.

Abstract: The present disclosure provides patterned biomaterials having organized cords and extracellular matrix embedded in a 3D scaffold. According, the present disclosure provides compositions and applications for patterned biomaterials. Pre-patterning of these biomaterials can lead to enhanced integration of these materials into host organisms, providing a strategy for enhancing the viability of engineered tissues by promoting vascularization.

Abstract: A nanoparticle activity sensor containing a reporter and at least one tuning domain that modifies a distribution or residence time of the activity sensor when administered to a patient. When administered to the patient, the activity sensor enters cells or tissue where it is cleaved by enzymes specific to a physiological state such as a disease to release a detectable analyte. The tuning domains include molecular structures that modulate distribution or decay by protecting the particle from premature cleavage and indiscriminate hydrolysis, shielding the particle from immune detection and clearance, or by targeting the particle to specific tissue, bodily fluids, or cell types.

Abstract: Methods and compositions for screening or diagnosis of liver disease are provided. The results may also indicate course and efficacy of treatment. The composition includes an activity sensor and a reporter releasably attached to the activity sensor. The method includes detecting the presence and/or amount of a reporter. The reporter is released from an activity sensor in the presence of diseased liver tissue but remains attached to the activity sensor in healthy tissue. The presence and/or amount of the reporter are used to characterize the liver disease. The liver disease may be nonalcoholic steatohepatitis (NASH) and results may further indicate staging of NASH.