The present invention provides a CpG oligonucleotide prodrug that includes a thermolabile substituent on at least one nucleotide thereof. The present invention also provides compositions that include a carrier and a therapeutically effective amount of at least one CpG oligonucleotide prodrug. The present invention further provides therapeutic methods of using such thermolabile CpG oligonucleotide prodrugs and compositions thereof. The present invention further provides a method of inhibiting tetrad formation in a CpG oligonucleotide by functionalizing the CpG oligonucleotide with one or more thermolabile substituents.

The addition of an oligodeoxynucleotide that is an avian TLR21 agonist, to an avian Herpesvirus vector vaccine, provides an acceleration of the immune response against the antigen that is expressed and delivered by the Herpesvirus vector.

The disclosure provides methods of producing neoantigens, comprising bringing a tumor cell culture in contact with an antisense oligonucleotide; and further, recovering the neoantigens; as well as immunogenic compositions comprising these neoantigens. The disclosure further provides methods of inducing an immune response in a subject against a cancer such as glioblastoma; and methods of treating a cancer such as glioblastoma in a subject comprising administering to the subject a therapeutically effective amount of the neoantigens and compositions disclosed herein.

The present invention is directed to a polymeric carrier cargo complex, comprising as a cargo at least one nucleic acid molecule and as a preferably non-toxic and non-immunogenic polymeric carrier disulfide-crosslinked cationic components for use as an immunostimulating agent or as an adjuvant, wherein the polymeric carrier cargo complex is administered in combination with at least one second nucleic acid molecule, which encodes a protein or peptide. The inventive polymeric carrier cargo complex administered in combination with the second nucleic acid molecule allows for both efficient transfection of nucleic acids into cells in vivo and in vitro and/or for induction of an innate and/or adaptive immune response, preferably dependent on the nucleic acid to be transported as a cargo and on the second nucleic acid molecule. The present invention also provides pharmaceutical compositions, particularly vaccines, comprising the inventive polymeric carrier cargo complex and the second nucleic acid molecule, as well as the use of the inventive polymeric carrier cargo complex and the second nucleic acid molecule for transfecting a cell, a tissue or an organism, as a medicament, for therapeutic purposes as disclosed herein, and/or as an immunostimulating agent or adjuvant, e.g. for eliciting an immune response for the treatment or prophylaxis of diseases as mentioned herein. Finally, the invention relates to kits containing the inventive polymeric carrier cargo complex and the second nucleic acid molecule, the inventive pharmaceutical composition and/or the inventive vaccine or any of its components in one or more parts of the kit.

Disclosed are compositions and methods for targeted treatment of TLR9-expressing cancers. In particular, disclosed herein are molecules or conjugates containing a TLR9 targeting ligand, such as a CpG oligodeoxynucleotide, and a cytotoxic nanoparticle that targets TLR9-expressing malignant cells. Also disclosed is a pharmaceutical composition comprising a molecule disclosed herein in a pharmaceutically acceptable carrier. Also disclosed is a method for treating a TLR9-positive cancer in a subject that involves administering to the subject a therapeutically effective amount of a disclosed pharmaceutical composition.

The present invention relates to immune-stimulating compositions comprising an immunestimulating compound covalently or non-convalently linked to glycogen-based nanoparticles. The immune stimulating compound may be a TLR agonist, dietary nucleotide, or combination thereof. The compositions can elicit a stronger, more robust, localized (intestine) and systemic immune response when delivered orally to aquatic species, than non-glycogen bound agonists and/or molecules.

Provided herein are oligomeric compounds with conjugate groups targeting apolipoprotein C-III (ApoCIII). In certain embodiments, the ApoCIII targeting oligomeric compounds are conjugated to N-Acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting ApoCIII for use in decreasing ApoCIII to treat, prevent, or ameliorate diseases, disorders or conditions related to ApoCIII. Certain diseases, disorders or conditions related to ApoCIII include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.

Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

The present invention relates to nucleic acid molecules containing spacers and methods of using the same.

The invention relates to use of TLR9 antagonist in a method for treating cancer and/or chronic infection by downregulating Clever-1 expression on alternatively activated immunosuppressive macrophages.