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 particle formulations and/or systems comprising one or more components of a CRISPR-Cas system, which are means for targeting sites for delivery. The delivery particle formulations of the invention are preferably nanoparticle delivery formulations and/or systems. 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 disclosure provides devices and uses thereof. A devices disclosed herein comprises a plurality of microneedles adapted to protrude from the device. In some embodiments, a device is dimensioned and constructed to carry a payload, so that the payload can be delivered to an internal tissue of a subject or through a wall of a vessel after interaction with microneedles. In some embodiments, devices can be used for oral or intravenous administration. In some embodiments, devices can be used for implantation such as vaginal, rectal, urethral or bladder suppository or pessary.

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: A cross-modal interface includes a multi-modal sensor configured to concurrently receive multiple input signals with each input signal being provided from a different imaging modality and in response thereto providing a single cross-modal output signal to processing circuitry which processes the single cross-modal output signal provided thereto and generates an output comprising information obtained or otherwise derived from each of or a combination of the different imaging modalities.

Abstract: Zwitterionic polymers or biocompatible polymers with improved properties for cell encapsulation, coating of devices, or a combination thereof are described. The biocompatible polymer contains a zwitterionic monomer, a monomer with a reactive side chain, and optionally another hydrophobic monomer or a neutral hydrophilic monomer. The zwitterionic polymers are cross-linked with a cross-linker via covalent bond to form a zwitterionic hydrogel in the presence of cells. Also provided, are methods of making and using the zwitterionic polymers.

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: 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: A composition containing biocompatible hydrogel encapsulating mammalian cells and anti-inflammatory drugs is disclosed. The encapsulated cells have reduced fibrotic overgrowth after implantation in a subject. The compositions contain a biocompatible hydrogel having encapsulated therein mammalian cells and anti-inflammatory drugs or polymeric particles loaded with anti-inflammatory drugs. The anti-inflammatory drugs are released from the composition after transplantation in an amount effective to inhibit fibrosis of the composition for at least ten days. Methods for identifying and selecting suitable anti-inflammatory drug-loaded particles to prevent fibrosis of encapsulated cells are also described. 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: Compositions and methods for modified dendrimer nanoparticle (“MDNP”) delivery of therapeutic, prophylactic and/or diagnostic agent such as large repRNA molecules to the cells of a subject have been developed. MDNPs efficiently drive proliferation of antigen-specific T cells against intracellular antigen, and potentiate antigen-specific antibody responses. MDNPs can be multiplexed to deliver two or more different repRNAs to modify expression kinetics of encoded antigens and to simultaneous deliver repRNAs and mRNAs including the same UTR elements that promote expression of encoded antigens.

Abstract: Disclosed are methods and constructs for engineering circular RNA. Disclosed is a vector for making circular RNA, said vector comprising the following elements operably connected to each other and arranged in the following sequence: a.) a 5? homology arm, b.) a 3? group I intron fragment containing a 3? splice site dinucleotide, c.) optionally, a 5? spacer sequence, d.) a protein coding or noncoding region, e.) optionally, a 3? spacer sequence, f) a 5? Group I intron fragment containing a 5? splice site dinucleotide, and g.) a 3? homology arm, said vector allowing production of a circular RNA that is translatable or biologically active inside eukaryotic cells. In another embodiment, the vector can comprise the 5? spacer sequence, but not the 3? spacer sequence. In yet another embodiment, the vector can comprise the 3? spacer sequence, but not the 5? spacer sequence.

Abstract: Compositions and methods for modified dendrimer nanoparticle (“MDNP”) delivery of therapeutic, prophylactic and/or diagnostic agent such as large repRNA molecules to the cells of a subject have been developed. MDNPs efficiently drive proliferation of antigen-specific T cells against intracellular antigen, and potentiate antigen-specific antibody responses. MDNPs can be multiplexed to deliver two or more different repRNAs to modify expression kinetics of encoded antigens and to simultaneous deliver repRNAs and mRNAs including the same UTR elements that promote expression of encoded antigens.

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: CGMs containing a sensor electrode that is partially or completely coated with one or more layers of a material containing zwitterionic polymers are disclosed. With just a single calibration after implantation, CGMs containing the zwitterionic polymer coatings show reduced discordance between detected and actual blood glucose levels, during the crucial first one to three days, where current commercially available CGMs tend to show discordance with actual blood glucose levels.

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: 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 the encapsulation and transplantation of cells. Also disclosed are high throughput methods for the characterizing the biocompatibility and physiochemical properties of modified alginate polymers.

Abstract: A composition containing biocompatible hydrogel encapsulating mammalian cells and anti-inflammatory drugs is disclosed. The encapsulated cells have reduced fibrotic overgrowth after implantation in a subject. The compositions contain a biocompatible hydrogel having encapsulated therein mammalian cells and anti-inflammatory drugs or polymeric particles loaded with anti-inflammatory drugs. The anti-inflammatory drugs are released from the composition after transplantation in an amount effective to inhibit fibrosis of the composition for at least ten days. Methods for identifying and selecting suitable anti-inflammatory drug-loaded particles to prevent fibrosis of encapsulated cells are also described. 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: The disclosure relates to compositions comprising and methods for chemical modification of single guide RNA (sgRNA), tracrRNA and/or crRNA used individually or in combination with one another or Cas system components. Compositions comprising modified ribonucleic acids have been designed with chemical modification for even higher efficiency as unmodified native strand of sgRNA. Administration of modified ribonucleic acids will allow decreased immune response when administered to a subject, increased stability, increased editing efficiency and facilitated in vivo delivery of sgRNA via various delivery platforms. The disclosure also relates to methods of decreasing off-target effect of CRISPR and a CRISPR complex.

Abstract: The present invention provides, in certain embodiments, compositions comprising a uniform population of free, single crystals of a hydrophobic compound. Methods of administering, and processes for preparing, compositions comprising a uniform population of free, single crystals of a hydrophobic compound are also provided.

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: 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 the encapsulation and transplantation of cells. Also disclosed are high throughput methods for the characterizing the biocompatibility and physiochemical properties of modified alginate polymers.