RNA encoding an immunogen is co-delivered to non-immune cells as the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g., by a single injection.

RNA encoding an immunogen is co-delivered to non-immune cells as the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g., by a single injection.

The present invention is directed to a method for modifying the retention time of RNA on a chromatographic column. The present invention also concerns a method for purifying RNA from a mixture of at least two RNA species. Furthermore, the present invention relates to a method for co-purifying at least two RNA species from a mixture of at least two RNA species. In particular, the present invention provides a method for harmonizing the numbers of A and/or U nucleotides in at least two RNA species. The present invention is also directed to RNA obtainable by said methods, a composition comprising said RNA or a vaccine comprising said RNA and methods for producing such RNA and compositions. Further, the invention concerns a kit, particularly a kit of parts, comprising the RNA, composition or vaccine. The invention is further directed to a method of treating or preventing a disorder or a disease, first and second medical uses of the RNA, composition and vaccine. Moreover, the present invention concerns a method for providing an adapted RNA sequence or an adapted RNA mixture.

Compositions and methods relating to modulating thermogenic regulation are disclosed. The compositions and methods can be used to treat diseases or conditions such as obesity or cardiometabolic disorders such as type 2 diabetes mellitus, NAFLD and NASH. Compositions include an adipocyte-targeting composition that includes a therapeutic agent capable of modulating thermogenic regulation, a targeting element facilitating cellular uptake and delivery of the therapeutic agent to a targeted adipocyte, and liposomal particles comprising sphingomyelin, DMPC, and cholesterol, wherein the liposomal particles enhance intra-cellular penetration of the therapeutic agent and protect the therapeutic agent from degradation.

Compositions and methods relating to modulating thermogenic regulation are disclosed. The compositions and methods can be used to treat diseases or conditions such as obesity or cardiometabolic disorders such as type 2 diabetes mellitus, NAFLD and NASH. Compositions include an adipocyte-targeting composition that includes a therapeutic agent capable of modulating thermogenic regulation, a targeting element facilitating cellular uptake and delivery of the therapeutic agent to a targeted adipocyte, and liposomal particles comprising sphingomyelin, DMPC, and cholesterol, wherein the liposomal particles enhance intra-cellular penetration of the therapeutic agent and protect the therapeutic agent from degradation.

Provided herein are methods and compositions for inhibiting p97, for the treatment of a coronavirus infection in a subject, or a symptom thereof. Upon treatment, the coronavirus infection, or a symptom thereof is reduced in the subject.

Provided herein are methods and compositions for inhibiting p97, for the treatment of a coronavirus infection in a subject, or a symptom thereof. Upon treatment, the coronavirus infection, or a symptom thereof is reduced in the subject.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to EGP-1 (TROP-2), CEACAM5, CEACAM6, CD74, CD19, CD20, CD22, CSAp, HLA-DR, AFP or MUC5ac and the immunoconjugate may be administered at a dosage of between 4 mg/kg and 24 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to EGP-1 (TROP-2), CEACAM5, CEACAM6, CD74, CD19, CD20, CD22, CSAp, HLA-DR, AFP or MUC5ac and the immunoconjugate may be administered at a dosage of between 4 mg/kg and 24 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

Aspects herein relate to systems and methods for delivery of biologic agents to the central nervous system. In various embodiments, a method of administering a therapeutic agent to the central nervous system (CNS) is included. The method can include injecting a therapeutic agent into a first cerebrospinal fluid (CSF) region of the subject. The method can further include establishing fluid communication between a fluid reservoir and a second cerebrospinal fluid (CSF) region of a subject, the fluid having a hydraulic pressure at or above an intracranial pressure. The method can further include infusing a hyperosmotic fluid systemically. Other embodiments, including kits and systems are also included herein.