Abstract: Glucose-responsive insulin conjugates that contain one or more trisaccharides are provided. Such insulin conjugates may display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose, even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule.

Abstract: The invention relates to stable formulations of cyclic dinucleotide STING agonist compounds or pharmaceutically acceptable salts thereof. The invention further provides methods for treating various cancers with stable formulations of the invention. In some embodiments of the methods of the invention, the formulations are administered to a subject by intratumoral or subcutaneous administration.

Abstract: The present invention relates to RNAi molecules, and compositions thereof, comprising a 2? internucleoside linkage connecting the nucleotide at position 1 and the nucleotide at position 2 at the 5? end of the antisense strand. Specifically, the invention relates to single- and double-stranded short interfering nucleic acid (siNA) molecules that are capable of mediating RNA interference comprising 5? modified nucleotides that comprise, among other potential modifications, a 2? internucleoside linkage. The invention further relates to 5? modified nucleotides used as reagents to generate the RNAi molecules of the invention and methods of using the disclosed RNAi molecules.

Abstract: The present invention relates to RNAi molecules, and compositions thereof, comprising a 2? internucleoside linkage connecting the nucleotide at position 1 and the nucleotide at position 2 at the 5? end of the antisense strand. Specifically, the invention relates to single- and double-stranded short interfering nucleic acid (siNA) molecules that are capable of mediating RNA interference comprising 5? modified nucleotides that comprise, among other potential modifications, a 2? internucleoside linkage. The invention further relates to 5? modified nucleotides used as reagents to generate the RNAi molecules of the invention and methods of using the disclosed RNAi molecules.

Abstract: Insulin conjugates comprising an insulin analog molecule covalently attached to at least one bi-dentate linker having two arms, each arm independently attached to a ligand comprising a saccharide and wherein the saccharide for at least one ligand of the linker is fucose are disclosed. The insulin conjugates display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule such as Con A.

Abstract: The present invention relates to RNAi molecules, and compositions thereof, comprising a 2? internucleoside linkage connecting the nucleotide at position 1 and the nucleotide at position 2 at the 5? end of the antisense strand. Specifically, the invention relates to single- and double-stranded short interfering nucleic acid (siNA) molecules that are capable of mediating RNA interference comprising 5? modified nucleotides that comprise, among other potential modifications, a 2? internucleoside linkage. The invention further relates to 5? modified nucleotides used as reagents to generate the RNAi molecules of the invention and methods of using the disclosed RNAi molecules.

Abstract: Insulin conjugates comprising an insulin molecule covalently attached to at least one bi-dentate linker having two arms, each arm independently attached to a ligand comprising a saccharide and wherein the saccharide for at least one ligand of the linker is fucose are disclosed. The insulin conjugates display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule such as Con A.

Abstract: The present invention relates to RNAi molecules, and compositions thereof, comprising a 2? internucleoside linkage connecting the nucleotide at position 1 and the nucleotide at position 2 at the 5? end of the antisense strand. Specifically, the invention relates to single- and double-stranded short interfering nucleic acid (siNA) molecules that are capable of mediating RNA interference comprising 5? modified nucleotides that comprise, among other potential modifications, a 2? internucleoside linkage. The invention further relates to 5? modified nucleotides used as reagents to generate the RNAi molecules of the invention and methods of using the disclosed RNAi molecules.

Abstract: Insulin conjugates comprising an insulin molecule covalently attached to at least one bi-dentate linker having two arms, each arm independently attached to a ligand comprising a saccharide and wherein the saccharide for at least one ligand of the linker is fucose are disclosed. The insulin conjugates display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule such as Con A.

Abstract: The present invention provides poly(amide) polymers, polyconjugates, compositions and methods for the delivery of oligonucleotides for therapeutic purposes.

Abstract: The present invention provides poly(amide) polymers, polyconjugates, compositions and methods for the delivery of oligonucleotides for therapeutic purposes.