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: 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: Methods and constructs for engineering circular RNA are disclosed. In some embodiments, the methods and constructs comprise a vector for making circular RNA, the 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, the vector allowing production of a circular RNA that is translatable or biologically active inside eukaryotic cells. Methods for purifying the circular RNA produced by the vector and the use of nucleoside modifications in circular RNA produced by the vector are also disclosed.

Abstract: Methods and constructs for engineering circular RNA are disclosed. In some embodiments, the methods and constructs comprise a vector for making circular RNA, the 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, the vector allowing production of a circular RNA that is translatable or biologically active inside eukaryotic cells. Methods for purifying the circular RNA produced by the vector and the use of nucleoside modifications in circular RNA produced by the vector are also disclosed.

Abstract: Methods and constructs for engineering circular RNA are disclosed. In some embodiments, the methods and constructs comprise a vector for making circular RNA, the 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, the vector allowing production of a circular RNA that is translatable or biologically active inside eukaryotic cells. Methods for purifying the circular RNA produced by the vector and the use of nucleoside modifications in circular RNA produced by the vector are also disclosed.

Abstract: Circular RNA and transfer vehicles, along with related compositions and methods are described herein. In some embodiments, the inventive circular RNA comprises group I intron fragments, spacers, an IRES, duplex forming regions, and an expression sequence. In some embodiments, the expression sequence encodes a chimeric antigen receptor (CAR). In some embodiments, circular RNA of the invention has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, inventive methods and constructs result in improved circularization efficiency, splicing efficiency, and/or purity when compared to existing RNA circularization approaches.

Abstract: Methods and constructs for engineering circular RNA are disclosed. In some embodiments, the methods and constructs comprise a vector for making circular RNA, the 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, the vector allowing production of a circular RNA that is translatable or biologically active inside eukaryotic cells. Methods for purifying the circular RNA produced by the vector and the use of nucleoside modifications in circular RNA produced by the vector are also disclosed.

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: 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: The present disclosure relates to compositions and methods for modifying a gene sequence, and for systems for deliverying such compositions. For example, the disclosure relates to modifying a gene sequence using a CRISPR-Cas9 or other nucleic acid editing system, and methods and delivery systems for achieving such gene modification, such as viral or non-viral delivery systems.

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: 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: 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: 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: The present disclosure relates to compositions and methods for modifying a gene sequence, and for systems for delivering such compositions. For example, the disclosure relates to modifying a gene sequence using a CRISPR-Cas9 or other nucleic acid editing system, and methods and delivery systems for achieving such gene modification, such as viral or non-viral delivery systems.

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: 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 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: 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.