Abstract: The invention provides a cell library for use in detecting protein expression comprising a plurality of cells, wherein each cell comprises a polynucleotide sequence encoding a detectable marker integrated into the genome of the cell in frame with a protein coding gene selected from a set of target genes, wherein the library comprises more than one cell tagged at each target gene, as well as a cell library for use in detecting protein interactions between a protein of interest and a set of target proteins and a cell library for use in detecting protein modifications. The invention also provides methods of constructing a cell library for use in proteomics, as well as methods for sequencing integration sites of a donor sequence inserted into the genome of a cell. Also provided are systems for analysis of proteins in a cell and kits comprising vectors for tagging a population of cells and for performing proteomics studies.

Abstract: Oligonucleotides bearing free, uncapped 5? phosphate group(s) are recognized by RIG-I, leading to the induction of type I IFN, IL-18 and IL-1? production. Bacterial RNA also induces type I IFN production. 5? phosphate oligonucleotides and bacterial RNA can be used for inducing an anti-viral response or an anti-bacterial response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in vitro and in vivo and for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, tumors, allergies, autoimmune diseases, immunodeficiencies and immunosuppression. Single-stranded 5? triphosphate RNA can be used for inducing an anti-viral response, an anti-bacterial response, or an anti-tumor response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in a target cell-specific manner.

Abstract: The present invention pertains to novel treatments for cancer diseases. Treatment of cancers with nucleoside analogs (NA), which specifically inhibit rapidly dividing cells, may face preexisting NA resistance or development of resistant cancer cells resulting in poor clinical prognosis. Treatment of cancers with oncolytic herpes simplex viruses (HSV) may face preexisting resistance or development of resistant cancer cells resulting in poor clinical prognosis. The invention overcomes chemotherapy resistance or resistance to oncolytic HSV by providing methods for detecting the resistance in a cancer disease based on the expression of SAM domain and HD domain-containing protein 1 (SAMHD1) in cancer cells. Furthermore provided are treatment options addressing the chemotherapy resistance such as a combination of a SAMHD1 inhibitor with a NA. Moreover, provided are treatment options addressing the resistance to oncolytic HSV such as a combination of a SAMHD1 inhibitor or depletion of SAMHD1 with an oncolytic HSV.

Abstract: The present invention is directed to methods and kits for gene analysis. The methods of the invention comprise the steps of providing nucleic acid; synthesis of a single-stranded DNA that is complementary to said nucleic acid molecule by contacting the nucleic acid with a DNA polymerase, a primer and a mixture of dNTPs under conditions that allow the generation of the DNA, wherein the primer comprises a target-complementary region and wherein the dNTP mixture comprises dATP, dGTP, dCTP, dTTP and dUTP; cleaving the DNA 5? to dU sites by (i) contacting the DNA with an uracil deglycosylase to generate a basic sites at positions of dUTP incorporation in the DNA; and (ii) contacting the DNA with an apurinic/apyrimidinic (AP) endonuclease; contacting the DNA comprising at its 5?-end the nucleotide sequence of the primer with a ssDNA ligase to circularize the DNA; and sequencing the circularized cDNA. The kits comprise the components necessary to perform the methods of the invention.

Abstract: Oligonucleotides bearing free, uncapped 5? phosphate group(s) are recognized by RIG-I, leading to the induction of type I IFN, IL-18 and IL-1? production. Bacterial RNA also induces type I IFN production. 5? phosphate oligonucleotides and bacterial RNA can be used for inducing an anti-viral response or an anti-bacterial response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in vitro and in vivo and for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, tumors, allergies, autoimmune diseases, immunodeficiencies and immunosuppression. Single-stranded 5? triphosphate RNA can be used for inducing an anti-viral response, an anti-bacterial response, or an anti-tumor response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in a target cell-specific manner.

Abstract: The present invention is directed to methods and kits for gene analysis. The methods of the invention comprise the steps of providing nucleic acid; synthesis of a single-stranded DNA that is complementary to said nucleic acid molecule by contacting the nucleic acid with a DNA polymerase, a primer and a mixture of dNTPs under conditions that allow the generation of the DNA, wherein the primer comprises a target-complementary region and wherein the dNTP mixture comprises dATP, dGTP, dCTP, dTTP and dUTP; cleaving the DNA 5? to dU sites by (i) contacting the DNA with an uracil deglycosylase to generate a basic sites at positions of dUTP incorporation in the DNA; and (ii) contacting the DNA with an apurinic/apyrimidinic (AP) endonuclease; contacting the DNA comprising at its 5?-end the nucleotide sequence of the primer with a ssDNA ligase to circularize the DNA; and sequencing the circularized cDNA. The kits comprise the components necessary to perform the methods of the invention.

Abstract: Oligonucleotides bearing free, uncapped 5? phosphate group(s) are recognized by RIG-I, leading to the induction of type I IFN, IL-18 and IL-1? production. Bacterial RNA also induces type I IFN production. 5? phosphate oligonucleotides and bacterial RNA can be used for inducing an anti-viral response or an anti-bacterial response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in vitro and in vivo and for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, tumors, allergies, autoimmune diseases, immunodeficiencies and immunosuppression. Single-stranded 5? triphosphate RNA can be used for inducing an anti-viral response, an anti-bacterial response, or an anti-tumor response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in a target cell-specific manner.

Abstract: The present invention provides 4-nucleotide (4mer) RNA motifs that confer immunostimulatory activity, in particular, IL-12-inducing activity to a single-stranded RNA oligonucleotide. The present invention also provides single-stranded RNA oligonucleotides, including antisense RNA, with high or low immunostimulatory activity. The present invention further provides the use of the RNA oligonucleotides of the invention for therapeutic purposes.

Abstract: Provided herein are methods of identifying and using compounds that modulate an AIM2 polypeptide-mediated immune response. Further provided herein are methods of treating disease comprising administering to a patient a compound that decreases expression of an AIM2 polypeptide. Further provided herein are methods of providing gene therapy to a patient comprising administering to the patient a gene therapy agent and a compound that decreases expression of an AIM2 polypeptide. In certain embodiments, a compound that decreases expression of an AIM2 polypeptide comprises an siRNA or an shRNA.

Abstract: Oligonucleotides bearing free, uncapped 5? phosphate group(s) are recognized by RIG-I, leading to the induction of type I IFN, IL-18 and IL-1? production. Bacterial RNA also induces type I IFN production. 5? phosphate oligonucleotides and bacterial RNA can be used for inducing an anti-viral response or an anti-bacterial response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in vitro and in vivo and for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, tumors, allergies, autoimmune diseases, immunodeficiencies and immunosuppression. Single-stranded 5? triphosphate RNA can be used for inducing an anti-viral response, an anti-bacterial response, or an anti-tumor response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in a target cell-specific manner.

Abstract: The present invention provides 4-nucleotide (4mer) RNA motifs that confer immunostimulatory activity, in particular, IFN-?-inducing activity to a RNA oligonucleotide. The present invention also provides RNA oligonucleotides, including siRNA, with high or low immunostimulatory activity. The present invention further provides the use of the RNA oligonucleotides of the invention for therapeutic purposes.

Abstract: Tis invention provides oligonucleotide agents that modulate an immune response by stimulating IFN production and methods of using such agents for therapeutic treatments of mammals.

Abstract: The present invention provides 4-nucleotide (4mer) RNA motifs that confer immunostimulatory activity, in particular, IFN-?-inducing activity to a RNA oligonucleotide. The present invention also provides RNA oligonucleotides, including siRNA, with high or low immunostimulatory activity. The present invention further provides the use of the RNA oligonucleotides of the invention for therapeutic purposes.

Abstract: This invention provides oligonucleotide agents that modulate an immune response by stimulating IFN production and methods of using such agents for therapeutic treatments of mammals.

Abstract: Oligonucleotides bearing free, uncapped 5? phosphate group(s) are recognized by RIG-I, leading to the induction of type I IFN, IL-18 and IL-1? production. Bacterial RNA also induces type I IFN production. 5? phosphate oligonucleotides and bacterial RNA can be used for inducing an anti-viral response or an anti-bacterial response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in vitro and in vivo and for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, tumors, allergies, autoimmune diseases, immunodeficiencies and immunosuppression. Single-stranded 5? triphosphate RNA can be used for inducing an anti-viral response, an anti-bacterial response, or an anti-tumor response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in a target cell-specific manner.

Abstract: Methods of treating an inflammatory disorder and inhibiting inflammation by administering an inhibitor of a pH-activated protease are provided.

Abstract: Provided herein are methods of identifying and using compounds that modulate an AIM2 polypeptide-mediated immune response. Further provided herein are methods of treating disease comprising administering to a patient a compound that decreases expression of an AIM2 polypeptide. Further provided herein are methods of providing gene therapy to a patient comprising administering to the patient a gene therapy agent and a compound that decreases expression of an AIM2 polypeptide. In certain embodiments, a compound that decreases expression of an AIM2 polypeptide comprises an siRNA or an shRNA.

Abstract: The present invention provides 4-nucleotide (4mer) RNA motifs that confer immunostimulatory activity, in particular, IFN-?-inducing activity to a RNA oligonucleotide. The present invention also provides RNA oligonucleotides, including siRNA, with high or low immunostimulatory activity. The present invention further provides the use of the RNA oligonucleotides of the invention for therapeutic purposes.

Abstract: The present invention provides 4-nucleotide (4mer) RNA motifs that confer immunostimulatory activity, in particular, IL-12-inducing activity to a single-stranded RNA oligonucleotide. The present invention also provides single-stranded RNA oligonucleotides, including antisense RNA, with high or low immunostimulatory activity. The present invention further provides the use of the RNA oligonucleotides of the invention for therapeutic purposes.

Abstract: This invention provides oligonucleotide agents that modulate an immune response by stimulating IFN production and methods of using such agents for therapeutic treatments of mammals.