Abstract: The present disclosure is in the field of genome engineering, particularly targeted modification of the genome of a cell.

Abstract: Herpes simplex virus (HSV) including herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are a persistent cause of human disease with no known cure. Guided nuclease systems target specific regions of the HSV-1 and HSV-2 genomes, disrupting the virus' nucleic acid and rendering even latent viruses incapacitated.

Abstract: The invention provides compositions and methods for treating human papillomavirus (HPV) infections using a targetable nuclease, which compositions and methods can be used to selectively target the HPV genome or selectively express the targetable nuclease within cells that infected by HPV. By selectively targeting cells infected by HPV, the HPV genome within infected cells, or both, the nuclease is able to cleave the HPV genome thereby inactivating it and rendering it inoperable, interfering with the virus's ability to propagate even where the virus is in a latent stage of infection. Since latent HPV can be cleaved and eradicated from the host cells, compositions and methods of the invention may be used to treat HPV infections and potentially prevent many of the adverse health consequences associated with the papillomavirus.

Abstract: The invention provides delivery methods and compositions for antiviral therapeutics. Methods and compositions are provided for targeted delivery of antiviral therapeutics into cells of interest using, for example, viral vectors such as adenovirus, AAV, and replication incompetent HSV. These and other delivery systems can be used as vehicles to deliver DNA vectors encoding a nuclease or a cell-killing gene. These delivery methods can also be used to deliver naked DNA or RNA, protein products, plasmids containing a promoter that is active only in a latent viral state which drives a cell-killing gene, or other therapeutic agents.

Abstract: Methods and compositions comprising a CRISPR/Cas nuclease that cleaves a T cell receptor (TCR) gene and/or human leukocyte (HLA) gene, the nuclease comprising a cleavage domain and a single guide RNA that binds to a target site in the TCR and/or HLA gene.

Abstract: Methods and compositions comprising a CRISPR/Cas nuclease that cleaves a BCL11A gene for the modification of the BCL11A gene and for modification of globin expression.

Abstract: Disclosed herein are methods and compositions for generating a single-stranded break in a target sequence, which facilitates targeted integration of one or more exogenous sequences.

Abstract: Viral infection is a persistent cause of human disease. Guided nuclease systems target the genomes of viral infections, rendering the viruses incapacitated.

Abstract: Viral infection is a persistent cause of human disease. Guided nuclease systems of the invention target the genomes of viral infections, rendering the viruses incapacitated. The invention further provides delivery methods and compositions for antiviral therapeutics. Methods and compositions are provided for targeted delivery of antiviral therapeutics into cells of interest using, for example, viral vectors such as adenovirus, AAV, and replication incompetent HSV. These and other delivery systems can be used as vehicles to deliver DNA vectors encoding a nuclease or a cell-killing gene. These delivery methods can also be used to deliver naked DNA or RNA, protein products, plasmids containing a promoter that is active only in a latent viral state which drives a cell-killing gene, or other therapeutic agents.

Abstract: A parallelized multiple dispatch ordered queue including an ordered queue, qualify logic, ordered select logic, and dispatch logic. The ordered queue stores candidates in order from oldest to youngest into multiple entries. The ordered queue is divided into N groups in which an i'th group includes every i'th entry of every N entries of the ordered queue, wherein i is an integer less than or equal to N. The qualify logic determines whether any candidate is ready to be dispatched. The ordered select logic respectively determines the oldest candidate in each group that is ready to be dispatched. The dispatch logic dispatches the oldest ready candidates in parallel. The shift logic shifts the stored candidates in the ordered queue to fill any vacant entries between remaining ones of the stored candidates without changing an order of the remaining ones of the stored candidates in the ordered queue. The ordered queue may have any size or depth and N is any suitable integer determining the number of candidates (e.g.

Abstract: Herpes simplex virus (HSV) including herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are a persistent cause of human disease with no known cure. Guided nuclease systems target specific regions of the HSV-1 and HSV-2 genomes, disrupting the virus' nucleic acid and rendering even latent viruses incapacitated.

Abstract: Disclosed herein are methods and compositions for generating a single-stranded break in a target sequence, which facilitates targeted integration of one or more exogenous sequences.

Abstract: The invention provides delivery methods and compositions for antiviral therapeutics. Methods and compositions are provided for targeted delivery of antiviral therapeutics into cells of interest using, for example, viral vectors such as adenovirus, AAV, and replication incompetent HSV. These and other delivery systems can be used as vehicles to deliver DNA vectors encoding a nuclease or a cell-killing gene. These delivery methods can also be used to deliver naked DNA or RNA, protein products, plasmids containing a promoter that is active only in a latent viral state which drives a cell-killing gene, or other therapeutic agents.

Abstract: The present disclosure is in the field of genome engineering, particularly targeted modification of the genome of a cell.

Abstract: Methods and compositions comprising single guide RNAs targeted to endogenous gene for genetic alteration of cells are provided.

Abstract: Methods and compositions for comprising single guide RNAs targeted to an endogenous gene for genetic alteration of cells are provided.

Abstract: The present disclosure is in the field of genome engineering, particularly targeted modification of the genome of a cell.

Abstract: Methods and compositions comprising a fusion protein comprising a Cas protein and a functional domain in association with a single guide RNA targeted to an endogenous gene for genetic alteration of cells are provided.

Abstract: Methods and compositions comprising single guide RNAs targeted to an endogenous mammalian ? globin gene (HBB), gamma globin gene (HBG1), B-cell lymphoma/leukemia 11A (BCL11A) gene, Kruppel-like factor 1 (KLF1) gene, CCR5 gene, CXCR4 gene, PPP1R12C (AAVS1) gene, hypoxanthine phosphoribosyltransferase (HPRT) gene, albumin gene, Factor VIII gene, Factor IX gene, Leucine-rich repeat kinase 2 (LRRK2) gene, Hungtingin (Htt) gene, rhodopsin (RHO) gene, Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, surfactant protein B gene (SFTPB), T-cell receptor alpha (TRAC) gene, T-cell receptor beta (TRBC) gene, programmed cell death 1 (PD1) gene, Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) gene, human leukocyte antigen (HLA) A gene, a LMP7 gene, a Transporter associated with Antigen Processing (TAP) gene, tapasin gene (TAPBP), a class II major histocompatibility complex transactivator (CIITA) gene, a dystrophin gene (DMD), a glucocorticoid receptor gene (GR), IL2RG gene or RFX5 for genetic alteration of cells a

Abstract: Methods are provided for diagnosis and prognosis of disease by analyzing expression of a set of genes obtained from single cell analysis. Classification allows optimization of treatment, and determination of whether on whether to proceed with a specific therapy, and how to optimize dose, choice of treatment, and the like. Single cell analysis also provides for the identification and development of therapies which target mutations and/or pathways in disease-state cells.