The present invention relates to a peptide and its use as a medicament, in particular in the treatment of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD) or cholestatic liver disease.

The disclosure pertains to conformational epitopes in alpha-synuclein, antibodies thereto and methods of making and using immunogens and antibodies specific thereto. In particular antibodies raised to cyclic compounds comprising at least 3 amino acids of EKTKEQ (SEQ ID NO: 1) selectively recognize misfolded oligomeric alpha-synuclein and are able to inhibit alpha-synuclein propagation and toxicity.

The disclosure pertains to conformational epitopes in alpha-synuclein, antibodies thereto and methods of making and using immunogens and antibodies specific thereto. In particular antibodies raised to cyclic compounds comprising at least 3 amino acids of EKTKEQ (SEQ ID NO: 1) selectively recognize misfolded oligomeric alpha-synuclein and are able to inhibit alpha-synuclein propagation and toxicity.

The disclosure features fusion proteins that are conditionally active variants of a cytokine of interest. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g. a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling. Typically, the fusion proteins further comprise an in vivo half-life extension element, which may be cleaved from the cytokine in the tumor microenvironment.

The disclosure features fusion proteins that are conditionally active variants of a cytokine of interest. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g. a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling. Typically, the fusion proteins further comprise an in vivo half-life extension element, which may be cleaved from the cytokine in the tumor microenvironment.

Provided herein are regulatable expression systems and methods of using said regulatable expression systems to express proteins of interest. The regulatable expression systems comprise a unidirectional regulatable promoter operably linked to a single transcription unit encoding a protein of interest, a ribosome skip, and a transactivator protein.

Provided is a fusion polypeptide comprising GDF15 (Growth/differentiation factor 15) and an Fc region of immunoglobulin, a pharmaceutical composition comprising the fusion polypeptide, and a method of increasing in vivo duration of GDF15 comprising fusing with an Fc region of immunoglobulin.

Provided is a fusion polypeptide comprising GDF15 (Growth/differentiation factor 15) and an Fc region of immunoglobulin, a pharmaceutical composition comprising the fusion polypeptide, and a method of increasing in vivo duration of GDF15 comprising fusing with an Fc region of immunoglobulin.

One aspect described herein is use of a compound to modulate the production of one or more mature RNA isoforms from a gene transcript in a cell. Another aspect described herein is use of a compound in a method to modulate exon inclusion or exon exclusion in one or more mature mRNA isoforms from a gene transcript in a cell.

The invention relates to logic-gate-based Type II or Type V CRISPR-Cas constructs and methods for modifying gene expression using the CRISPR-Cas constructs and CRISPR-Cas effector proteins.