Abstract: Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for engineering Cas9 and Cas9 variants that have increased activity on target sequences that do not contain the canonical PAM sequence. In some embodiments, fusion proteins comprising such Cas9 variants and nucleic acid editing domains, e.g., deaminase domains, are provided.

Abstract: RNA molecules comprising a guide sequence portion having 17-25 contiguous nucleotides containing nucleotides in the sequence set forth in any one of SEQ ID NOs: 1-6601 and compositions, methods, and uses thereof.

Abstract: The invention provides a polynucleotide sequence (e.g., a gene, e.g., DNA or RNA) encoding UGT1A1 (e.g., expressing human UGT1A1). The invention further provides a vector, such as an adeno-associated virus (AAV) vector (e.g., AAV8) having a vector genome including inverted terminal repeat sequences and a UGT1A1 coding sequence operably linked to one or more expression control sequences (e.g., expression control sequences including a liver-specific promoter). Also provided are compositions containing these AAV vectors and methods of treating Crigler-Nijjar syndrome type I, Crigler-Nijjar syndrome type II, and Gilbert syndrome.

Abstract: Methods of detecting, probing, mapping and directed sequencing of target nucleic acids are provided using a guide RNA and a Cas9 protein. Methods for detecting the binding of the guide RNA/Cas9 complex to a target nucleic acid where the guide RNA includes a 3? tail sequence that can hybridize to a probe are provided. Methods for detecting the binding of the guide RNA/Cas9 complex to a target nucleic acid where the complex is physically detected are provided.

Abstract: A method of treating or preventing a microbial infection in a patient is provided, along with a wound irrigation system and a composition in the form of an irrigation liquid for reducing microbial load or preventing microbial infection in a wound.

Abstract: The present invention relates to an artificially manipulated neovascularization-associated factor for regulating neovascularization and a use thereof. More particularly, the present invention relates to a system for artificially regulating neovascularization, which includes an artificially manipulated neovascularization-associated factor for regulating neovascularization and/or a composition for artificially manipulating the neovascularization-associated factor. In a specific aspect, a neovascularization regulatory system including a neovascularization-associated factor such as artificially manipulated VEGFA, HIF1A, ANGPT2, EPAS1, or ANGPTL4 and/or an expression product thereof is provided.

Abstract: The disclosure provides methods for treating or limiting development age-related macular degeneration, comprising (a) a GPR143 receptor agonist, including but not limited to L-DOPA, L-DOPA analogues, or a pharmaceutically acceptable salt thereof, and (b) melatonin, a melatonin analogue, or a pharmaceutically acceptable salt thereof, and related compositions.

Abstract: Temperature sensitive transcriptional bioswitches and related genetic circuits and in particular bandpass and/or multiplex genetic circuits, vectors, cells, compositions methods and systems are described.

Abstract: A method of treating or preventing a microbial infection in a patient is provided, along with a wound irrigation system and a composition in the form of an irrigation liquid for reducing microbial load or preventing microbial infection in a wound.

Abstract: Provided are binding molecules, such as TCRs or antigen binding fragments thereof and antibodies and antigen-binding fragments thereof, such as those that recognize or bind human papilloma virus (HPV) 16, including HPV 16 E6 and HPV 16 E7. Also provided are engineered cells containing such binding molecules, compositions containing the binding molecules or engineered cells, and methods of treatment, such as administration of the binding molecules, engineered cells, or compositions.

Abstract: The invention provides improved methods, compositions, and kits for detecting ploidy of chromosome regions, e.g. for detecting cancer or a chromosomal abnormality in a gestating fetus. The methods can utilize a set of more than 200 SNPs that are found within haploblocks and can include analyzing a series of target chromosomal regions related to cancer or a chromosomal abnormality in a gestating fetus. Finally the method may use knowledge about chromosome crossover locations or a best fit algorithm for the analysis. The compositions may comprise more than 200 primers located within haplotype blocks known to show CNV.

Abstract: The present invention relates to a tissue-specific promoter system for expressing microRNA (miRNA) for RNA interference-based methods of gene therapy. In these systems, the miRNA will inhibit gene expression or replace natural miRNA expression using microRNA.

Abstract: Provided herein are compositions, systems, and methods for extracting and detecting at least one HDL-associated protein (e.g., ApoA1) from a sample (e.g., plasma or serum sample). In certain embodiments, a strong organic acid and hydrophilic organic solvent are mixed with the sample; after centrifugation, the supernatant is transferred to a second container where it is mixed with a non-polar organic solvent; after centrifugation, the lower aqueous layer is transferred to a third container; and then at least a portion of the transferred aqueous layer is subjected to a detection assay such that at least one HDL-associated protein is detected.

Abstract: Systems and methods are provided for transfecting immune competent cells with RNA at high efficiency and viability.

Abstract: The present invention provides novel methods and systems, including cell lines, recombinant polynucleotide constructs, compositions, and kits, for targeted yet universal genomic manipulation.

Abstract: Provided herein are isolated neural stem cells and methods of making neural stem cells from human trophoblast stem cells. The isolated neural stem cells can be immune privileged and express one or more protein(s). Also provided are methods for treatment of neurodegenerative diseases using suitable preparations comprising the isolated neural stem cells.

Abstract: Aspects of the disclosure relate to recombinant gene editing complexes comprising a recombinant gene editing protein and guide RNA (gRNA) that specifically hybridizes to a region of a C90RF72 gene (e.g., a region flanking a G4C2 repeat or within a exonic region of the gene).

Abstract: The ?c-family cytokines, Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-7 (IL-7), Interleukin-9 (IL-9), Interleukin-15 (IL-15), and Interleukin-21 (IL-21), are associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of ?c-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. Peptide and/or peptide derivative antagonists based on the consensus ?c-subunit binding site to inhibit ?c-cytokine activity are described. Also described are peptide and/or peptide derivative antagonists exhibiting Simul-Block activity, and inhibiting the activity of multiple ?c-cytokine family members.

Abstract: Methods for design of genetic circuits are provided.

Abstract: Compounds, pharmaceutical compositions, and a method of treating hard tissue diseases and disorders are disclosed. The compounds may be a peptide and is structured to bind integrin ?v?3 expressed by osteocytes and by selective binding to the cell surface integrin on hard tissue forming cells regulate three-dimensional bone shape, cartilage formation and repair.