The present invention relates to a protein having proteolytic activity inducible and activable by the experimenter in the cytosol or in the secretory pathway, and uses thereof for controlling the maturation in a vital cell of a protein subject to proteolytic cleavage, and in a purification process of recombinant proteins.

Synthetic alphavirus-derived replicon expression systems comprising nucleic acid sequences encoding at least one modified nonstructural protein, and synthetic nucleic acid sequences encoding at least one heterologous protein are described. Methods of producing at least one heterologous protein in a cell, or of inducing an immune response in a subject by administering and/or expressing the synthetic alphavirus-derived replicon expression systems are provided.

Provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof expressing a polyethylene glycol (PEG) receptors and methods of using the same. Also provided are compositions, polypeptides, vectors, and methods of manufacturing.

Provided are an oncolytic virus and an application thereof, and a drug for treating a cancer. A first regulatory element and a second regulatory element are inserted into the genome of the oncolytic virus. The first regulatory element comprises a tumor-specific promoter and a first nucleic acid sequence, which is driven by the cancer cell specific promoter to express a specific protease in tumor cells; the second regulatory element comprises a second nucleic acid sequence for encoding an extracellular secretion signal peptide and a third nucleic acid sequence for encoding a specific cleavage site. The oncolytic virus can be replicated in tumor cells effectively to kill tumor cells while being safe to non-cancer cells.

Provided is a proteolysis-targeting virus, wherein one or more proteolysis-targeting molecules that can be recognized by the ubiquitin-proteasome system are comprised at one or more different sites of protein thereof, and the viral protein is linked to the proteolysis-targeting molecules by one or more linkers that can be selectively cleaved. Also provided are a nucleic acid molecule encoding the proteolysis-targeting virus, a nucleic acid vector expressing the proteolysis-targeting virus, a preparation method for the proteolysis-targeting virus, methods for the preparation of an attenuated live virus, replication-incompetentlive virus, replication-controllable live virus, and a relevant vaccine and medication for preventing and treating virus infections, a vaccine or pharmaceutical composition comprising the proteolysis-targeting virus, and a system for preparing the proteolysis-targeting virus.

Flavivirus virus-like particles (VLPs) are provided that display on their surfaces antigenic flavivirus proteins. The VLPs include at least one flavivirus structural protein and at least one non-structural flavivirus protein. A DNA construct that includes sequences encoding flavivirus viral proteins used to assemble the flavivirus VLP is also provided. A method of producing flavivirus VLPs by introducing one or more the DNA constructs into a host cell is also provided. An immunogenic composition that includes the flavivirus VLP is also provided.

It is intended to provide a fusion polypeptide that regulates the transcription of a target gene. The present inventors have provided a fusion polypeptide comprising: a cell-penetrating peptide; a DNA-binding polypeptide; and a transcriptional regulator.

Provided are fusion proteins and related molecules useful for conducting base editing with reduced or no off-target mutations. The fusion proteins may include a first fragment comprising a nucleobase deaminase or a catalytic domain thereof, a second fragment comprising a nucleobase deaminase inhibitory domain, and a protease cleavage site between the first fragment and the second fragment. Also provided are improved prime editing systems, including prime editing guide RNA with improved stability.

Synthetic alphavirus-derived replicon expression systems comprising nucleic acid sequences encoding at least one modified nonstructural protein, and synthetic nucleic acid sequences encoding at least one heterologous protein are described. Methods of producing at least one heterologous protein in a cell, or of inducing an immune response in a subject by administering and/or expressing the synthetic alphavirus-derived replicon expression systems are provided.

Described herein are engineered fusion proteins comprising a variant protease (e.g., an HCV NS3 protease) fused to a polypeptide of interest and a cognate protease cleavage site. The cleavability of the cognate protease cleavage site enables the controllability of one or more functions of the polypeptide of interest. Additionally disclosed are methods for generating engineered fusion proteins as well as their therapeutic use.