Abstract: The present invention provides compounds, e.g., compounds of Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are implantable elements (e.g., devices and materials) comprising the same, as well as methods of use thereof, e.g., for treating or preventing a disease, disorder, or condition.

Abstract: The present disclosure relates to implantable constructs and related compositions comprising a plurality of cells producing antigens and/or immune effector molecules.

Abstract: The present disclosure relates to implantable constructs (encapsulated cells) designed to deliver therapeutic reagents, such as IL-12 and/or IL-12 and methods of using the same to treat conditions, such as cancer.

Abstract: The present disclosure relates to implantable constructs (encapsulated cells) designed to deliver antigenic therapeutic reagents, such as IL-2.

Abstract: The present disclosure provides expression constructs designed to provide for expression of therapeutic proteins from engineered cells. The engineered cells may be encapsulated into implantable elements that allow for the therapeutic protein to be released into from the capsule while protecting the cell from the immune system of a patient into which the capsule is implanted.

Abstract: Described herein are RPE cells engineered to secrete a FVII protein, as well as compositions, pharmaceutical preparations, and implantable devices comprising the engineered RPE cells, and methods of making and using the same for treating a patient with hemophilia or FVII deficiency.

Abstract: Provided herein are high-throughput methods for genetic barcoding and analysis, e.g., for tagging each biomaterial apsule with a barcode cell. These barcode cells are derived from patient samples, and thus embody natural human genetic variation. Also provided are SNP panels that can be used as genetic barcodes to identify the identity of a cell.

Abstract: The present disclosure provides expression constructs designed to provide for stable and/or inducible, tightly controlled production of genetically encoded payloads from engineered cells. These cassettes allow cells to be engineered to express genetically encoded payloads despite epigenetic silencing. As such, provided herein are expression systems for use in methods to engineer cells using CRISPR dCas9-activator systems such that expression of genetically encoded payloads (e.g., therapeutic proteins) can be optimized to overcome epigenetic silencing. In addition, provided herein are engineered cells comprising the expression systems.

Abstract: The present disclosure relates to implantable constructs designed to deliver antigenic therapeutic reagents to a subject while providing protection from host immune responses. In certain aspects, the constructs are designed to degrade over time or upon a particular signal, thereby providing control of the length of time the therapeutic agent is delivered to the subject.

Abstract: Biomedical devices for implantation with decreased pericapsular fibrotic overgrowth are disclosed. The device includes biocompatible materials and has specific characteristics that allow the device to elicit less of a fibrotic reaction after implantation than the same device lacking one or more of these characteristic that are present on the device. Biocompatible hydrogel capsules encapsulating mammalian cells having a diameter of greater than 1 mm, and optionally a cell free core, are disclosed which have reduced fibrotic overgrowth after implantation in a subject. Methods of treating a disease in a subject are also disclosed that involve administering a therapeutically effective amount of the disclosed encapsulated cells to the subject.

Abstract: Described herein are RPE cells engineered to secrete a GLA protein, as well as compositions, pharmaceutical preparations, and implantable devices comprising the engineered RPE cells, and methods of making and using the same for treating Fabry disease.

Abstract: The disclosure describes new devices and methods for vascularizing devices and methods for implanted diagnostics and therapeutics. The present disclosure provides, in certain embodiments, a device containing a degradable shell and a non-degradable core. In certain embodiments, the non-degradable core can include encapsulated therapeutic cells and/or biosensors, wherein the degradable shell serves as a scaffold for blood vessel growth, resulting in enhanced blood flow to the cells and/or biosensors.

Abstract: Neurological implants whose surfaces have been chemically and covalently modified to impart beneficial properties to the neurological implants are described. The neurological implants possess improved biocompatibility compared to a corresponding neurological implant that lacks the chemical modification. Following implantation in a subject, the surface-modified neurological implants induce a lower-foreign body response, compared to a corresponding unmodified product.

Abstract: Polyarginine-coated nanoparticle, and methods for making and using the nanoparticle. The nanoparticle can have a core that includes a material that imparts magnetic resonance imaging activity to the particle and, optionally, include one or more of an associated therapeutic agent, targeting agent, and diagnostic agent.

Abstract: Covalently modified alginate polymers, possessing enhanced biocompatibility and tailored physiochemical properties, as well as methods of making and use thereof, are disclosed herein. The covalently modified alginates are useful as a matrix for coating of any material where reduced fibrosis is desired, such as encapsulated cells for transplantation and medical devices implanted or used in the body.

Abstract: Provided herein are methods for quantifying foreign cell-free DNA (cfDNA) via SNP profiling of low-volume blood sample. The methods allow for monitoring the status of organ transplant rejection through analysis of small volumes of patient capillary blood samples collected non-invasively with fingersticks or other devices. The methods also allow for guiding the dosage of immunosuppressant and for preparing for a new organ transplant in case of imminent organ failure.

Abstract: Covalently modified alginate polymers, possessing enhanced biocompatibility and tailored physiochemical properties, as well as methods of making and use thereof, are disclosed herein. The covalently modified alginates are useful as a matrix for coating of any material where reduced fibrosis is desired, such as encapsulated cells for transplantation and medical devices implanted or used in the body.

Abstract: Described herein are implantable devices comprising means for mitigating the foreign body response (FBR) and at least one cell-containing compartment which comprises a plurality of cells (e.g., live cells) encapsulated in a polymer composition comprising a cell-binding substance (CBS), as well as compositions and methods of making and using the same. The cells are capable of expressing a therapeutic agent useful for the treatment of a disease, disorder, or condition described herein.

Abstract: Surface-modified cell containing a cell and a conformal coating on the extracellular surface of the cell are described. The conformal coating contains two or more layers containing particles (e.g. nanoparticles) or macromolecules. The cell is an islet cell, a B cell, or a T cell. The macromolecules or particles are formed from zwitterionic polymers. Covalent linkages are employed to link the particles or macromolecules to a cell surface molecule containing an abiotic functional group, or between macromolecules and/or particles in adjacent layers. Also described are methods of making and using a surface-modified cell.

Abstract: Covalently modified alginate polymers, possessing enhanced biocompatibility and tailored physiochemical properties, as well as methods of making and use thereof, are disclosed herein. The covalently modified alginates are useful as a matrix for coating of any material where reduced fibrosis is desired, such as encapsulated cells for transplantation and medical devices implanted or used in the body.