This invention provides compositions, compounds, and uses thereof, wherein said compounds comprise a single strand oligonucleotide that may form a short oligonucleotide hairpin or stem loop molecule with self complementary base pairing of less than 12 base pairs that bind to RIG-I and activate the RIG-I pathway.

The present invention relates to nucleic acids of the general formula (I): (N.sub.uG.sub.lX.sub.mG.sub.nN.sub.v).sub.a and derivatives thereof as an immunostimulating agent/adjuvant and to compositions containing same, optionally comprising an additional adjuvant. The present invention furthermore relates to a pharmaceutical composition or to a vaccine, each containing nucleic acids of formula (I) above and/or derivatives thereof as an immunostimulating agent, and optionally at least one additional pharmaceutically active component, e.g. an antigenic agent. The present invention relates likewise to the use of the pharmaceutical composition or of the vaccine for the treatment of cancer diseases, infectious diseases, allergies and autoimmune diseases etc. Likewise, the present invention includes the use of nucleic acids of the general formula (I): (N.sub.uG.sub.lX.sub.mG.sub.nN.sub.v).sub.a and/or derivatives thereof for the preparation of a pharmaceutical composition for the treatment of such diseases.

The present disclosure pertains to the recognition that immune responses mediated by CpG oligonucleotides can be affected by the stereochemistry of modified internucleotidic linkages such as phosphorothioates. In some embodiments, the present disclosure relates to chirally controlled CpG oligonucleotide compositions comprising CpG oligonucleotides comprising multiple modified internucleotidic linkages such as phosphorothioate linkages, wherein the oligonucleotides comprise one or more CpG region motifs having defined stereochemistry patterns of chiral internucleotidic linkages. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are capable of agonizing an immune response. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are antagonistic. Methods for making and using chirally controlled CpG oligonucleotide compositions are also described. In some embodiments, no immune modulation is desired, and the present disclosure provides methods of identifying chirally controlled oligonucleotide compositions which have decreased immune modulation.

Disclosed herein are CpG conjugated nanoparticles for immunotherapy and photothermal therapy. The composition comprises class B CpG conjugated nanoparticles and/or a class C CpG conjugated nanoparticles where the class B CpG conjugated nanoparticles comprises a nanoparticle core and a class B CpG conjugated thereto and the class C CpG conjugated nanoparticles comprises a nanoparticle core and a class C CpG conjugated thereto.

The present invention relates to RNA, particularly an immunostimulatory RNA (isRNA), a coding RNA or a combination thereof, for use in the treatment or prophylaxis of a disease, in particular a tumor and/or cancer disease. The present invention also provides pharmaceutical compositions, and a kit comprising the RNA(s). Further, the invention also comprises medical uses of the RNA(s) and compositions comprising the RNA(s).

Cancer immunotherapies effective for treating tumors are disclosed. A cytosolic receptor that detects viral ribonucleic acid (RNA), retinoic-acid-inducible protein 1 (RIG-I), is activated by a synthetic double-stranded oligonucleotide pUUC Auk. In one implementation, RIG-I is activated by a single-stranded oligonucleotide agonist formulated with a squalene emulsion (SE) adjuvant. Activation of RIG-I with pUUC Auk results in slower tumor growth. Formulation with a SE adjuvant increases the ability of RIG-I agonists to slow tumor growth. The novel agonist and formulations provided herein are effective for slowing the growth of new tumors and reducing further growth of established tumors. RIG-I agonist/adjuvant formulations may be administered to a subject by any of multiple routes including intratumoral injection.

The invention relates to a composition comprising a double-stranded RNA (dsRNA) having two complementary strands, comprising at least one block of poly A and the complementary block of poly U, each strand having a length of between 50 and 200 bases, preferably between 55 and 200 bases, and a pharmaceutically acceptable vehicle, carrier or excipient, for use in a method of treating a cancer expressing a TLR3 receptor.

Disclosed is a method for treating endometriosis, preventing endometriosis, or ameliorating a symptom of endometriosis in a subject comprising the step of administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising as an active ingredient a therapeutic dsRNA (tdsRNA).

Disclosed is a method for treating a cancer, such as pancreatic cancer, in a subject. The method comprises a first step of administering to the subject a standard of care therapy such as FOLFIRINOX and administering to the subject a therapeutic double stranded RNA (tdsRNA) which can be Rintatolimod.

The present invention provides an oligonucleotide comprising the sequence 5′-GGAACAGTTCGTCCATGGC-3′ (SEQ ID NO:2) for use in the treatment of an inflammatory bowel disease in a human subject via topical administration to the colon, wherein the subject has not been subjected to colonic cleaning prior to said administration.