The present application relates, in some aspects, to the development of an assay that uses cell survival and/or cell viability as a phenotypic identifier to positively select for agents that destabilize a protein of interest.

The disclosure is directed to an isolated polynucleotide encoding a modified picornavirus 3C protease, wherein the modified picornavirus 3C protease includes an altered secondary structure and one or more amino acid substitution(s) located at one or more amino acid position(s) corresponding to positions 16-25, 99-100 and 115-130 of a wild-type Fool-and-Mouth Disease Virus (FMDV) 3C protease, wherein the isolated polynucleotide encoding the modified picornavirus 3C protease, when transformed into and co-expressed in a host cell, enhances transgene expression of a P1 precursor polypeptide in comparison to an amount of P1 precursor polypeptide transgene expression exhibited in a host cell transformed and co-expressed with a control picornavirus 3C protease, wherein the one or more corresponding amino acid position(s) is/are identified by an alignment of the modified picornavirus 3C protease with the one or more of the wild type FMDV 3C protease(s). Methods for processing a picornavirus P1 precursor polypeptide into picornavirus viral proteins and/or virus-like particles using the isolated polynucleotides are also provided.

The invention relates generally to methods for preparing recombinant nucleosomes. In particular, the invention relates to methods for ligating a histone peptide onto a fully assembled recombinant nucleosome. The invention further relates to modified core histone proteins, histone peptides to be ligated to the modified core histone proteins, and fully assembled recombinant nucleosomes and libraries of recombinant nucleosomes prepared by the methods of the invention.

The present disclosure provides, in part, compositions and methods for transient removal of neutralizing antibodies directed to AAV vectors. Such compositions and methods expand the patient cohort eligible for gene therapy and also for redosing/re-administration of AAV in patients previously treated with AAV vectors.

The present invention relates to a nucleic acid molecule encoding a fusion protein, wherein the nucleic acid molecule comprises: (a) a first nucleic acid sequence encoding a first biosensor, wherein said first biosensor is a first molecule capable of interacting with a second molecule; (b) a second nucleic acid sequence encoding an effector-activating module, wherein the effector-activating module comprises a nucleic acid sequence encoding a first part of a protease, wherein said first part of the protease is capable of interacting with a second part of said protease to form an active form of said protease; (c) a third nucleic acid sequence encoding a third biosensor comprising a protease cleavage site, wherein the protease cleavage site is sterically occluded in the absence of a stimulus for said third biosensor and wherein the protease cleavage site becomes accessible in the presence of said stimulus.

Provided herein are modified caspase-9 polypeptides, and chimeric caspase-9 proteins containing the modified caspase-9 polypeptides. The disclosure further provides polynucleotides encoding these proteins, engineered host cells containing these polynucleotides and proteins, including host cells that co-express a chimeric antigen receptor, and methods of making and using the same.

The present invention relates to the use of a cysteine endoprotease or a malt extract to prevent or reduce the cloudiness of a cereal-based beverage, fermented or not.

The technology relates in part to methods for controlling elimination of therapeutic cells, for example, cells that express a chimeric antigen receptor. The technology further relates to a two-step method of controlling destruction of therapeutic cells in a patient following an adverse event. The two-step system may include a rapamycin or rapamycin analog-based level of control and a second, rimiducid, level of control. The technology also relates in part to methods for cell therapy using cells that express the inducible caspase polypeptide and the rapamycin-sensitive polypeptide, where the proportion of therapeutic cells eliminated by apoptosis is related to the choice and amount of the administered ligand.

Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of Cas9 and nucleic acid editing enzymes or enzyme domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 and nucleic acid editing enzymes or domains, are provided.

Disclosed are a gene expression cassette for expressing an N-terminal-methionine-truncated target protein comprising a nucleic acid encoding a target protein and a nucleic acid encoding a cysteine protease, in which a cysteine protease recognition sequence is inserted between methionine (Met), which is the first amino acid at the N-terminus of the target protein, and the second amino acid and N-terminal methionine is cleaved with the cysteine protease, and a method of producing an N-terminal-methionine-truncated target protein using the same.