The present invention provides a linear multimeric biomolecule polymer wherein a biomolecule is bonded to a polyubiquitin scaffold formed of two or more covalently bonded ubiquitins, by obtaining, from a host cell, a biomolecule bonded with a ubiquitin C-terminal tag through recombinant expression, and polyubiquitinating the biomolecule in vitro in the presence of proteins involved in ubiquitination, E1 (activation enzyme), E2 (conjugation enzyme), and E3 (ligase), and a substrate. The polymer according to the present invention may be used in the separation and purification of a biomolecule, the separation of a target material that binds to the biomolecule, etc.

Disclosed herein are multifunctional polypeptides comprising a first domain comprising an anti-tau antigen binding domain and a second domain comprising a proteasome-targeting PEST motif, and methods for using these polypeptides in treatment of tauopathies.

In one aspect, the invention features a method for identifying a drug-modulated polypeptide substrate of cereblon (CRBN). In another aspect, the invention features a method of identifying a polypeptide target of a modulator of CRBN. In yet another aspect, the invention provides methods of monitoring or characterizing the sensitivity of a subject to a modulator of CRBN.

Methods and compositions relating to an engineered peptide capable of binding to a biological molecule for viral inhibition. The engineered peptide is computationally-derived from soluble angiotensin-converting enzyme 2 (sACE2), a known receptor for viral spike proteins. The engineered peptide is optimized for minimal size and off-target effects. The engineered sACE2 peptide variants are a suitable targeting domain for fusion proteins of various effects.

In one aspect, the invention provides a peptide comprising a chaperone-mediated autophagy (CMA)-targeting signal domain; a protein-binding domain that selectively binds to a target cytosolic protein; and a cell membrane penetrating domain (CMPD). In another aspect, the invention provides methods for reducing the intracellular expression level of an endogenous target protein in vitro and in an animal, wherein the method involves administration of the peptide. Methods are also provided for treating a pathological condition in an animal, the methods comprising administering the peptide to the animal. In one embodiment, the pathological condition is a neurodegenerative disease. In another embodiment of the invention, the target cytosolic protein is death associated protein kinase I and the CMPD is protein transduction domain of the HIV-1 Tat protein.

A CRISPR/Cas system and method for editing or regulating transcription of a genome of a cell are provided, wherein the system includes a Cas endonuclease fused with one or more degron sequences and at least one activatable cognate single guide RNA harboring an inactivation sequence in a non-essential region of the cognate sgRNA, wherein said inactivation sequence comprises one or more endonuclease recognition sites of, e.g., a ribozyme.

The present invention relates to stable formulations of a cytomegalovirus (CMV) comprising for example, a genetically modified CMV that is conditionally replication defective, a buffer, alkali or alkaline salt, a sugar, a cellulose derivative and optionally a polyol.

The present disclosure provides compositions and methods comprising stabilized IL-18 polypeptides for use in therapeutic and non-therapeutic applications. In some cases, the stabilized IL-18 proteins provide IL-18 signaling activity even in the presence of an inhibitory molecule such as IL-18BP. Also provide are methods of administration and methods for making active polypeptides.

The present invention pertains to ubiquitin polypeptide variants (Ubvs) having improved affinity for 53BP1 relative to 53 ubiquitin polypeptide or i53 ubiquitin polypeptide, wherein the resultant interaction between the Ubvs and 53BP1 promotes increased homology directed repair of DNA double-strand break sites. Methods of suppressing 53BP1 recruitment to DNA double-strand break sites, increasing homologous recombination, increasing gene targeting, and editing a gene in a cell using a CRISPR system are provided with the Ubvs. Compositions and kits of Ubvs are also provided.

Disclosed herein are methods and compositions for inactivating TCR genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also provided. Disclosed herein are also methods and compositions for expressing a functional exogenous TCR in the absence of endogenous TCR expression in T lymphocytes, including lymphocytes with a central memory phenotype. Polynucleotides encoding exogenous TCR, vectors comprising polynucleotides encoding exogenous TCR and cells comprising polynucleotides encoding exogenous TCR and/or cells comprising exogenous TCR are also provided.