Cell-targeted cytotoxic agents, including sortase serine protease constructs, are provided. Such compounds can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant sortase serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity.

The invention relates to recombinant fusion proteins comprising a fibrinogenolytic enzyme having an amino acid sequence that is C-terminally and/or N-terminally linked to the amino acid sequence of at least one high-molecular inert stabilization domain with a molecular weight of >50 kDa, for the prevention or treatment of adhesions at tissues or organs, in particular peritoneal adhesions following surgical interventions.

The present disclosure relates to serine proteases and variants thereof. Compositions containing the serine proteases are suitable for use in cleaning fabrics and hard surfaces, as well as in a variety of industrial applications.

Described herein is an enzyme preparation including component (a): at least one compound according to general formula (I)

##STR00001## wherein R.sup.1 is; R.sup.2, R.sup.3, R.sup.4 are independently from each other selected from the group consisting of H, linear C.sub.1-C.sub.8 alkyl, and branched C.sub.3-C.sub.8 alkyl, C.sub.6-C.sub.10-aryl, non-substituted or substituted with one or more carboxylate or hydroxyl groups, and C.sub.6-C.sub.10-aryl-alkyl, wherein an alkyl of the C.sub.6-C.sub.10-aryl-alkyl is selected from the group consisting of linear C.sub.1-C.sub.8 alkyl and branched C.sub.3-C.sub.8 alkyl, wherein at least one of R.sup.2, R.sup.3, and R.sup.4 is not H, component (b): at least one enzyme selected from the group consisting of hydrolases (EC 3); and optionally component (c): at least one compound selected from the group consisting of solvents, enzyme stabilizers different from component (a), and compounds stabilizing the enzyme preparation.

A recombinant protein expressing one or more human growth factors, tumor antigens, and/or receptors or epitopes thereof on or within an immunogenic expression creating a recombinant protein in which one or more epitopes are presented on the surface of the sequence in their natural configuration. The growth factor, tumor antigen, and/or receptor, sequence(s) may be expressed within the encoding sequence at appropriate internal positions or at the termini as single expressions or as two or more tandem repeats.

The present invention is directed generally to cell-targeted cytotoxic constructs comprising a targeting polypeptide, a linking polypeptide and a cytotoxic polypeptide. Preferably, (a) the targeting polypeptide is a R-spondin1 (RSPO1), R-spondin2 (RSPO2) or yoked chorionic gonadotropin (YCG), the linking polypeptide comprises LPXT (SEQ ID NO: 56) or NPXT (SEQ ID NO: 60) as well as others, where X is any amino acid, the linking polypeptide being positioned between the targeting ligand and (c) the cytotoxic moiety is an auristatin or a truncated serine protease, the serine protease having an IIGG (SEQ ID NO: 91), IVGG (SEQ ID NO: 92) or ILGG (SEQ ID NO: 93) at its N-terminus. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer).

The present disclosure provides compositions and methods for treating, preventing, or inhibiting diseases of the eye. In one aspect, the disclosure provides recombinant CF1 adeno-associated virus (rAAV) vectors comprising a complement system gene.

Aspects of the disclosure relate to compositions and methods for multiplexed gene silencing in a cell or subject. In some embodiments, the disclosure provides an isolated nucleic acid or an rAAV encoding a transgene comprising a RNA-guided nuclease (RGN) operably linked to a first promoter, and a second promoter operably linked to a multi guide-RNA (multi-gRNA) expression cassette encoding one or more gRNAs targeting a gene associated with hypercholesterolemia or dyslipidemia. In some embodiments, the disclosure provides methods of treating a subject having hypercholesterolemia or dyslipidemia by administering the compositions.

The present invention relates to a novel cell-penetrating recombinant fusion protein including a peptide domain consisting of the amino acid sequence of SEQ ID NO: 1 and a peptide domain consisting of the amino acid sequence of SEQ ID NO: 2. The novel cell-penetrating cereblon recombinant fusion protein according to the present invention may be usefully employed in the prevention or treatment of cereblon-related diseases.

The present invention relates to means and methods for improving protease expression by co-expression with a foldase.