Described herein are antisense inhibitor adjuvant compositions comprising modified nucleotide sequences complementary to a Homo sapiens interleukin 10 (IL-10) or interleukin 10 receptor alpha (IL-10RA) genes and methods for use thereof.

In certain aspects, the present invention provides methods for inducing a stable gene modification of a target nucleic acid via homologous recombination in a primary cell, such as a primary blood cell and/or a primary mesenchymal cell. In certain other aspects, the present invention provides methods for enriching a population of genetically modified primary cells having targeted integration at a target nucleic acid. The methods of the present invention rely on the introduction of a DNA nuclease such as a Cas polypeptide and a homologous donor adeno-associated viral (AAV) vector into the primary cell to mediate targeted integration of the target nucleic acid. Also provided herein are methods for preventing or treating a disease in a subject in need thereof by administering to the subject any of the genetically modified primary cells or pharmaceutical compositions described herein to prevent the disease or ameliorate one or more symptoms of the disease.

Provided herein are composition for sensitizing tumors to anti-tumor therapies. The compositions include antisense oligonucleotides against TGFβ2, wherein the compositions sensitize tumors to anti-tumor therapies. Also provided herein are methods for treating cancer using the compositions described herein.

The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount, activity, or expression of the target nucleic acid in a cell. In certain embodiments, hybridization results in selective modulation of the amount, activity, or expression of a target Huntingtin gene or Huntingtin transcript in a cell.

The present invention relates to compositions and methods of use thereof for inhibiting mutant HTT mRNA transcription or CAG-expanded HTT protein expression in a cell, comprising contacting the cell with an effective amount of an oligomer targeting a differentiating polymorphism, wherein the differentiating polymorphism is selected from rs72239206, rs363107, rs362313, rs2530595, rs113407847. Specific oligomer sequences are also provided.

The invention relates to double stranded ribonucleic acid (dsRNA) agents and compositions targeting a High Density Lipoprotein Binding Protein (Hdlbp/Vigilin) gene, as well as methods of inhibiting expression of Hdlbp/Vigilin and methods of treating subjects having a disorder of lipid metabolism, such as mixed hyperlipidemia, hypertriglyceridemia or hypercholesterolemia, using such dsRNA agents and compositions.

The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the coronavirus genome. The invention also relates to methods of using such RNAi agents to inhibit expression of a coronavirus genome and to methods of treating or preventing a coronavirus-associated disease in a subject.

The present invention includes compositions and methods for the treatment of a medical condition or disease utilizing editing oligonucleotides. The editing oligonucleotides contain a an oligonucleotide strand of about 10 to about 50 nucleotides on each side of the editing moiety which may contain a sugar or linker that positions the active editing moiety in the proper location for hybridization to the target nucleic acid. The editing oligonucleotides may also contain at least one nucleotide sequence change from the targeted sequence in the genome. The method includes modifying a genomic sequence within a cell utilizing an editing oligonucleotide without additional proteins or nucleic acids to assist in the editing process. The editing oligonucleotide may comprise backbone modifications that increase the nuclease stability of the oligonucleotide as compared to unmodified oligonucleotides or oligonucleotides having three phosphorothioates on each terminus.

In certain aspects, the present invention provides methods for inducing a stable gene modification of a target nucleic acid via homologous recombination in a primary cell, such as a primary blood cell and/or a primary mesenchymal cell. In certain other aspects, the present invention provides methods for enriching a population of genetically modified primary cells having targeted integration at a target nucleic acid. The methods of the present invention rely on the introduction of a DNA nuclease such as a Cas polypeptide and a homologous donor adeno-associated viral (AAV) vector into the primary cell to mediate targeted integration of the target nucleic acid. Also provided herein are methods for preventing or treating a disease in a subject in need thereof by administering to the subject any of the genetically modified primary cells or pharmaceutical compositions described herein to prevent the disease or ameliorate one or more symptoms of the disease.

The invention relates to double stranded ribonucleic acid (dsRNA) agents and compositions targeting a High Density Lipoprotein Binding Protein (Hdlbp/Vigilin) gene, as well as methods of inhibiting expression of Hdlbp/Vigilin and methods of treating subjects having a disorder of lipid metabolism, such as mixed hyperlipidemia, hypertriglyceridemia or hypercholesterolemia, using such dsRNA agents and compositions.