This disclosure relates to oligonucleotides, compositions and methods useful for reducing PCSK9 expression, particularly in hepatocytes. Disclosed oligonucleotides for the reduction of PCSK9 expression may be double-stranded or single-stranded, and may be modified for improved characteristics such as stronger resistance to nucleases and lower immunogenicity. Disclosed oligonucleotides for the reduction of PCSK9 expression may also include targeting ligands to target a particular cell or organ, such as the hepatocytes of the liver, and may be used to treat hypercholesterolemia, atherosclerosis, and/or one or more symptoms or complications thereof.

An injectable peptide-based hydrogel is disclosed that incorporates a peptide inhibitor of proprotein convertase subtilisn/kexin type 9. The hydrogel is a polymer composed of the 13-amino-acid protein, Pep2-8, (TVFTSWEEYLDWV) attached to a self-assembling peptide of the ABA block structure (ESLSLSLSLSLSLEG) to generate the repeating multidomain peptide sequence (ESLSLSLSLSLSLEGTVFTSWEEYLDWV).

A vaccine is disclosed that promotes CD4+ T cell-independent host defense mechanisms to defend against infection by fungi such as Pneumocystis spp. The vaccine may be used to prevent or to treat fungal infections. The novel vaccine can provide protective immunity, even for immunocompromised individuals such as HIV patients having reduced levels of CD4+ T cells.

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

Provided is a long-acting PCSK9-specific binding protein and application thereof. Provided is an MV072 protein with unique complementarity-determining regions, i.e., a binding protein specifically binding to proprotein convertase subtilisin kexin type 9 (PCSK9). The protein can specifically bind to PCSK9, effectively inhibit the function of PCSK9 and reduce plasma LDL cholesterol level. Further provided is an application of the binding protein in treating diseases related to or influenced by the function of PCSK9.

Provided herein are cyclic polypeptide compounds that can, e.g., bind specifically to human proprotein convertase subtilisin/kexin type 9 (PCSK9) and optionally also inhibit interaction between human PCSK9 and human low density lipoprotein receptor (LDLR), and pharmaceutical compositions comprising one or more of these compounds. Also provided are methods of reducing LDL cholesterol level in a subject in need thereof that include administering to the subject one or more of the cyclic polypeptide compounds or a pharmaceutical composition provided herein.

Method of lowering low-density lipoprotein cholesterol or preventing a cardiac event in a subject who has atherosclerotic cardiovascular disease or who is atherosclerotic cardiovascular disease risk equivalent, involving administering to the subject a prophylactically effective amount of an RNAi agent. Also, a method of preventing development of atherosclerotic cardiovascular disease in a subject involving administering to the subject a prophylactically effective amount of an RNAi agent. Further, a method of treating a subject who has atherosclerotic cardiovascular disease or who is atherosclerotic cardiovascular disease risk equivalent involving administering to the subject a therapeutically effective amount of an RNAi agent.

The present invention relates to nanoparticles associated with (e.g., complexed, conjugated, encapsulated, absorbed, adsorbed, admixed) biomacromolecule agents configured for treating, preventing or ameliorating various types of disorders, and methods of synthesizing the same. In particular, the present invention is directed to compositions comprising nanoparticles (e.g., synthetic high density lipoprotein (sHDL)) associated with (e.g., complexed, conjugated, encapsulated, absorbed, adsorbed, admixed) biomacromolecule agents (e.g., nucleic acid, peptides, glycolipids, etc.), methods for synthesizing such nanoparticles, as well as systems and methods utilizing such nanoparticles (e.g., in diagnostic and/or therapeutic settings).

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.

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.