The present invention relates to a vaccine capable to induce the formation of antibodies directed to PCSK9 in vivo.

The present embodiments provide methods, compounds, and compositions useful for inhibiting PCSK9 expression, which may be useful for treating, preventing, or ameliorating a disease associated with PCSK9.

The present disclosure provides methods related to inhibiting or treating pancreatitis in a subject in need thereof, which include the use of a proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor. The disclosed PCSK9 inhibitors and compositions including them can be used for treatment, inhibition, or prevention of pancreatitis in a subject. Treatment methods can include administering to the subject a therapeutically effective amount of a PCSK9 inhibitor.

The present invention provides a vaccine containing a complex of a peptide consisting of the amino acid sequence of SEQ ID NO: 1 and an epitope of a disease-causing biological protein such as DPP4, IL-17A, IgE, S100A9 or PCSK9, which vaccine uses a less antigenic carrier protein and is capable of inducing antibody production to serve as an effective vaccine.

Despite the notion that human CD8.sup.+ T cells are the final mediators of autoimmune -cell destruction in type 1 diabetes (T1D), none of their target epitopes has been demonstrated to be naturally processed and presented by cells. The inventors therefore performed an epitope discovery study combining HLA Class I peptidomics and transcriptomics strategies. Inflammatory cytokines increased -cell peptide presentation in vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known -cell antigens and several insulin granule proteins. PCSK2 was identified as a novel -cell antigen, which was processed into HLA-A2-restricted epitopes recognized by circulating nave CD8.sup.+ T cells in type 1 diabetic and healthy donors. Accordingly, the present invention relates to antigenic peptides derived from PCSK2 and uses thereof for the diagnosis and treatment of T1D.

Provided herein are multifunctional heteromer proteins. In specific embodiments is a heteromultimer that comprises: at least two monomeric proteins, wherein each monomeric protein comprises at least one cargo polypeptide, attached to a transporter polypeptide, such that said monomeric proteins associate to form the heteromultimer. These therapeutically novel molecules comprise monomers that function as scaffolds for the conjugation or fusion of therapeutic molecular entities resulting in the creation of bispecific or multivalent molecular species.

The present disclosure provides improved genome editing compositions and methods for editing a PCSK9 gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of hypercholesterolemia or a condition associated therewith.

The invention relates to dual targeting siRNA agents targeting a PCSK9 gene and a second gene, and methods of using dual targeting siRNA agents to inhibit expression of PCSK9 and to treat PCSK9 related disorders, e.g., hyperlipidemia.

The present application provides materials and methods for treating a patient with one or more conditions associated with PCSK9 whether ex vivo or in vivo. In addition, the present application provides materials and methods for editing and/or modulating the expression of PCSK9 gene in a cell by genome editing.

Provided herein are multifunctional heteromer proteins. In specific embodiments is a heteromultimer that comprises: at least two monomeric proteins, wherein each monomeric protein comprises at least one cargo polypeptide, attached to a transporter polypeptide, such that said monomeric proteins associate to form the heteromultimer. These therapeutically novel molecules comprise monomers that function as scaffolds for the conjugation or fusion of therapeutic molecular entities resulting in the creation of bispecific or multivalent molecular species.