Compositions containing lipid nanoparticles and nucleic acid therapeutic agents are disclosed. For example, calcium phosphate nanoparticles having a lipid coating are provided, wherein the calcium phosphate nanoparticles include a cyclic dinucleotide and the lipid coating includes phosphatidylserine. The compositions can be formulated for administration to the lungs of a subject via inhalation, or for administration via injection. Methods for the treatment of lung cancer and other cancers are also described. Targeted delivery of therapeutic agents such as cyclic dinucleotides to antigen presenting immune cells via the disclosed methods can elicit beneficial antitumor immunity.

Compositions containing lipid nanoparticles and nucleic acid therapeutic agents are disclosed. For example, calcium phosphate nanoparticles having a lipid coating are provided, wherein the calcium phosphate nanoparticles include a cyclic dinucleotide and the lipid coating includes phosphatidylserine. The compositions can be formulated for administration to the lungs of a subject via inhalation, or for administration via injection. Methods for the treatment of lung cancer and other cancers are also described. Targeted delivery of therapeutic agents such as cyclic dinucleotides to antigen presenting immune cells via the disclosed methods can elicit beneficial antitumor immunity.

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.

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.

This invention provides a method for the in vivo delivery of oligonucleotides. The invention utilizes the presence of one or plurality of HES linked to an oligonucleotide to deliver a nucleic acid sequence of interest into the cytoplasm of cells and tissues of live organisms. The delivery vehicle is nontoxic to cells and organisms. Since delivery is sequence-independent and crosses membranes in a receptor-independent manner, the delivered oligonucleotide can target complementary sequences in the cytoplasm as well as in the nucleus of live cells. Sequences of bacterial or viral origin can also be targeted. The method can be used for delivery of genes coding for expression of specific proteins, antisense oligonucleotides, siRNAs, shRNAs, Dicer substrates, miRNAs, anti-miRNAs or any nucleic acid sequence in a living organism. The latter include mammals, plants, and microorganisms such as bacteria, protozoa, and viruses.

This invention provides a method for the in vivo delivery of oligonucleotides. The invention utilizes the presence of one or plurality of HES linked to an oligonucleotide to deliver a nucleic acid sequence of interest into the cytoplasm of cells and tissues of live organisms. The delivery vehicle is nontoxic to cells and organisms. Since delivery is sequence-independent and crosses membranes in a receptor-independent manner, the delivered oligonucleotide can target complementary sequences in the cytoplasm as well as in the nucleus of live cells. Sequences of bacterial or viral origin can also be targeted. The method can be used for delivery of genes coding for expression of specific proteins, antisense oligonucleotides, siRNAs, shRNAs, Dicer substrates, miRNAs, anti-miRNAs or any nucleic acid sequence in a living organism. The latter include mammals, plants, and microorganisms such as bacteria, protozoa, and viruses.

The present disclosure provides antibody drug conjugates comprising STING modulators. Also provided are compositions comprising the antibody drug conjugates. The compounds and compositions are useful for stimulating an immune response in a subject in need thereof.

The present disclosure provides antibody drug conjugates comprising STING modulators. Also provided are compositions comprising the antibody drug conjugates. The compounds and compositions are useful for stimulating an immune response in a subject in need thereof.

The present disclosure relates to 3′3′-cyclic dinucleotides having a carbocyclic nucleotide and derivatives that can modulate the activity of the STING adaptor protein.

There is provided a composition for use in a therapeutic method of treatment of a subject suffering from a neurological disorder, said composition comprising: A) serine, glycine, betaine, N-acetylglycine, N-acetylserine, dimethylglycine, sarcosine and/or phosphoserine; B)N-acetyl cysteine, cysteine and/or cystine; C) carnitine, deoxycarnitine, gamma-butyrobetaine, 4-trimethylammoniobutanal, 3-hydroxy-N 6,N6,N 6-trimethyl-L-lysine, N6,N6,N6-trimethyl-L-lysine and/or lysine; and D) nicotinamide.