Abstract: CRISPR-based gene-drive system for inhibiting antibiotic resistance of bacteria, including Escherichia coli that efficiently copies a gRNA cassette and adjacent cargo that are flanked with sequences homologous to the targeted gRNA/Cas9 cleavage site. This “pro-active” genetic system (Pro-AG) functionally inactivates an antibiotic resistance marker on a high copy number plasmid with greater efficiency than control CRISPR-based methods. Pro-AG can effectively edit large plasmids or single-copy genomic targets, or introduce functional genes, with numerous applications to biotechnology and biomedicine.

Abstract: Provided herein are systems and methods for performing repair of mutant chromosomes in cells by using the homologous chromosome as a template for homology directed repair. Also provided herein are CopyCatcher systems, methods, and organisms for the study and measurement of homologous chromosome template repair and related mechanisms in cells and organisms.

Abstract: An active genetic approach to preferentially transmit allelic variants (allelic-drive) resulting from only a single or a few nucleotide alterations. Embodiments are provided for allelic-drive: one, copy-cutting, in which a non-preferred allele is selectively targeted for Cas9/guide RNA (gRNA) cleavage, and a more general approach, copy-grafting, that permits selective inheritance of a desired allele located at some distance from the gRNA cut site. A lethal mosaicism is provided that dominantly eliminates NHEJ-induced mutations and favors inheritance of functional cleavage-resistant alleles. These two efficient allelic-drive methods, enhanced by lethal mosaicism and a trans-generational drive process provide a shadow-drive, that are applicable to improvements in health and agriculture.

Abstract: Methods and compositions for treatment of cell-cell barrier associated conditions, such as caused by anthrax Edema toxin, by inhibiting receptor tyrosine kinase. The present invention provides methods of treating a cell-cell barrier disruption-associated condition in a subject comprising administering to a subject in need thereof a treatment effective amount of an inhibitor of insulin growth factor-1 receptor (IGF-1R) or IGF-1R down stream signaling.

Abstract: Described herein are methods and compositions for autocatalytic genome editing and neutralizing autocatalytic genome editing. The autocatalytic genome editing may be based on genomic integration of a construct containing multiple elements or on a trans-complementation approach, in which genetic elements can be propagated separately. The disclosure provides a method for autocatalytic genome editing based on the CRISPR/CAS9 system, and methods of use thereof, in animals, humans, and plants for eliminating pathogens, targeting suppression of crop pests, strategies to combat virus (e.g., HIV) and other diseases (e.g., cancer) caused by retrovirus, as well as to generate homozygous mutations that are transmitted to nearly all offspring.

Abstract: Methods and pharmaceutical compositions for treating diseases characterized by compromised epithelial or endothelial barrier integrity are provided. The pharmaceutical compositions include an effective amount a Epac/Rap1 signaling inhibitor. The methods include administering to a patient suffering from a disease characterized by compromised epithelial or endothelial barrier integrity a therapeutically effective amount of a Epac/Rap1 signaling inhibitor, such as ESI-09, SecinH3, Slit, or AG1024.

Abstract: Provided are systems, constructs, genetically modified organisms, and methods for greatly reducing or eliminating local populations of Aedes aegypti mosquitoes, and associated Dengue fever, yellow fever, Zika virus, and Chikungunya virus. Provided are genetically modified Aedes aegypti having a Cas9-mediated split gene-drive system for masculinizing the mosquito and ensuring that any female carries a sterile mutation. In addition, gRNAs direct Cas9 cleavage of insecticide-resistance loci, rendering female mosquitoes escaping the male converting gene drive sensitive to insecticides.

Abstract: Provided are systems, constructs, genetically modified organisms, and methods for creating transgenic rodent research and commercial models of human physiology, disease, syndromes, and disorders. Provided are genetically modified rodents encoding for an sgRNA useful in a Cas9-mediated split gene-drive system for optimization of the gene drive system in rodents.

Abstract: Described herein are methods and compositions for autocatalytic genome editing and neutralizing autocatalytic genome editing. The autocatalytic genome editing may be based on genomic integration of a construct containing multiple elements or on a trans-complementation approach, in which genetic elements can be propagated separately. The disclosure provides a method for autocatalytic genome editing based on the CRISPR/CAS9 system, and methods of use thereof, in animals, humans, and plants for eliminating pathogens, targeting suppression of crop pests, strategies to combat virus (e.g., HIV) and other diseases (e.g., cancer) caused by retrovirus, as well as to generate homozygous mutations that are transmitted to nearly all offspring.

Abstract: Methods and pharmaceutical compositions for treating diseases characterized by compromised epithelial or endothelial barrier integrity are provided. The pharmaceutical compositions include an effective amount a Epac/Rap1 signaling inhibitor. The methods include administering to a patient suffering from a disease characterized by compromised epithelial or endothelial barrier integrity a therapeutically effective amount of a Epac/Rap1 signaling inhibitor, such as ESI-09, SecinH3, Slit, or AG1024.

Abstract: The invention provides methods for autocatalytic genome editing based on genomic integration of a construct containing multiple elements. More specifically, the invention provides a method for autocatalytic genome editing or for deleting or neutralizing autocatalytic genome editing based on the CRISPR/Cas9 system, and methods of use thereof, in animals, humans, and plants for eliminating pathogens, targeting suppression of crop pests, strategies to combat virus (e.g., HIV) and other diseases (e.g., cancer) caused by retrovirus, as well as to generate, and reverse, homozygous mutations that are transmitted to nearly all offspring.

Abstract: Method and composition for protection and treatment against influenza viral infection by modulating the activity of at least one essential host signaling pathways, including the Hedgehog (Hh), the Bone Morphogenetic Protein (BMP), the Notch (N) signaling pathways or combinations thereof, which activity is altered by the viral protein NS1. The method and composition comprise use of a compound that modulates at least one of these essential host signaling pathways for preventing or controlling symptoms associated with influenza viral infection. The method or composition can also be used either alone or in combination with other therapeutic agents for treating or protecting against influenza infection, and associated syndromes.

Abstract: Methods for generating and using novel overexpression activity alleles of a gene in any organism, especially Drosophilia, are provided. Such alleles may be utilized in screening assays, and used to generate dominant-negative forms of bacterial toxins.

Abstract: A potent peptide inhibitor (SuperSog) of TGF-? family growth factor signaling, peptide variants thereof and nucleotide coding sequences therefore are provided by the invention. The Super-Sog peptide comprises a fragment of the Drosophilia short gastrulation (Sog) gene which includes the CR-1 cysteine-rich repeat of Sog. Methods and compositions for use of Super-Sog in therapeutic and diagnostic applications are also provided.

Abstract: Methods for generating and using novel overexpression activity alleles of a gene in any organism, especially Drosophilia, are provided. Such alleles may be utilized in screening assays, and used to generate dominant-negative forms of bacterial toxins.

Abstract: Methods for generating and using novel overexpression activity alleles of a gene in any organism, especially Drosophilia, are provided. Such alleles may be utilized in screening assays, and used to generate dominant-negative forms of bacterial toxins.

Abstract: A potent peptide inhibitor (SuperSog) of TGF-? family growth factor signaling, peptide variants thereof and nucleotide coding sequences therefore are provided by the invention. The Super-Sog peptide comprises a fragment of the Drosophilia short gastrulation (Sog) gene which includes the CR-1 cysteine-rich repeat of Sog. Methods and compositions for use of Super-Sog in therapeutic and diagnostic applications are also provided.

Abstract: A potent peptide inhibitor (SuperSog) of TGF-&bgr; family growth factor signalling, peptide variants thereof and nucleotide coding sequences therefor are provided by the invention. The Super-Sog peptide comprises a fragment of the Drosophilia short gastrulation (Sog) gene which includes the CR-1 cysteine-rich repeat of Sog. Methods and compositions for use of Super-Sog in therapeutic and diagnostic applications are also provided.

Abstract: Methods for generating and using novel overexpression activity alleles of a gene in any organism, especially Drosophilia, are provided. Such alleles may be utilized in screening assays, and used to generate dominant-negative forms of bacterial toxins.