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.

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.

Provided herein are systems comprising Class2, Type V CRISPR polypeptides, guide nucleic acids (gNA), and optionally donor template nucleic acids useful in the modification of a PCSK9 gene. The systems are also useful for introduction into cells, for example eukaryotic cells having mutations in the PCSK9 gene. Also provided are methods of using such CasX:gNA systems to modify cells having such mutations.

Disclosed are compounds of Formula I, or a salt thereof: ##STR00001##
where A, B, D, X, R.sup.1, R.sup.2 and R.sup.8 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions.

Provided in the present disclosure is a fused protein. The fused protein comprises a plurality of target protein sequences, which are connected in series, wherein every two adjacent target protein sequences are connected by means of a linker sequence, the linker sequence is suitable for being cut into a plurality of free target proteins by means of protease, the multiple target protein sequences are not cleaved by the protease, and neither the C-terminus nor the N-terminus of the free target proteins contains additional residues.

Nucleic acid products that modulate, interfere with, or inhibit PCSK9 and APOC3 gene expression are provided, together with compositions containing the constructs and methods for their use.

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.

The invention belongs to the biopharmaceutical. It involves the role and mechanism of PCSK9 in inflammatory immune diseases, and the application of PCSK9 inhibitors to the preparation of drugs for the treatment of inflammatory immune diseases mediated by T cells. In particular, it involves the use of PCSK9 monoclonal antibody, PCSK9 interference RNA and PCSK9 small molecule inhibitors for treating psoriasis, atopic dermatitis, or urticaria. The invention uses psoriasis as an embodiment for the study of inflammatory and immune diseases. It is found that PCSK9 plays an important role in the treatment of inflammatory immune diseases. The PCSK9 monoclonal antibody, PCSK9 interference RNA, and PCSK9 small molecule inhibitor can be further developed for treating inflammatory immune-diseases, such as psoriasis with fewer adverse reactions, at low cost, and with good efficacy.

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 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.