A non-infections bacteriophage T4 nanoparticle vaccine composition includes a bacteriophage capsid and at least one antigen displayed on the surface of the capsid or packaged in its interior. The vaccine is administered intranasally and is free of an adjuvant. The antigen is selected from respiratory viruses including coronavirus and influenza.

Described herein are engineered, non-naturally occurring systems and compositions comprising multimeric CRISPR-Cas complexes comprising a -CASP polypeptide, a plurality of Cas polypeptides, and a guide molecule, packaging and delivery systems thereof, and methods of use thereof, for modifying target polynucleotides. In addition, described herein are engineered, non-naturally occurring systems and compositions comprising a class of small Cas proteins (Type II-B, II-C, and II-D Cas proteins) and methods of modifying target sequences using the Type II-B, II-C, II-D Cas proteins and systems thereof.

The present disclosure provides an isolated mammalian cell comprising a reduced or eliminated expression of Serine Hydroxymethyltransferase 2 (SHMT2). Further provided are methods for preparing such cells and methods for using such cells for the production of recombinant proteins.

Provided are epigenetic-modifying DNA-targeting systems, such as CRISPR-Cas/guide RNA (gRNA) systems, that bind to or target a target site in a gene or regulatory element thereof in a T cell. In some aspects, the provided epigenetic modifying DNA-targeting systems modulate a T cell function, such as a T cell phenotype or activity. In some aspects, also provided herein are methods and uses related to the provided compositions, for example in modulating T cells including in connection with methods of adoptive T cell therapy.

A method for predicting endophenotypes of interacting partner genes includes obtaining one or more endophenotype profiles corresponding to a genotype, partitioning the one or more endophenotype profiles into a first set of endophenotypes and a second set of endophenotypes, and receiving an input to modify the first set of endophenotypes to a desired level. The method thus includes inputting the modified first set of endophenotypes and unmodified second set of endophenotypes into a trained machine-learning model to obtain a prediction of an updated second set of endophenotypes. The updated second set of endophenotypes represents an updated version of the second set of endophenotypes after interacting with the modified subset of the first set of endophenotypes.

The present disclosure relates to a method for loading a dimeric CD24 into an HEK293 cell exosome with ADAM10 gene knocked out. By means of loading a dimeric CD24 and/or ApoE protein into an HEK293 cell exosome with ADAM10 gene knocked out, the efficacy is improved over 1000 times compared with that of a free CD24-Fc fusion protein and ApoE protein. Meanwhile, a MyD88 inhibitor polypeptide is loaded into the exosome, so that the inhibition efficacy of the exosome on an inherent immune inflammatory response is improved. After the CD24-exosome, the ApoE-exosome, or the CD24-ApoE-exosome loaded with the described inhibitor polypeptide is phagocytosed and removed by an immune cell, the MyD88 inhibitor polypeptide can be released in the cell, the inflammation inhibition efficacy is continuously exerted, and the duration of drug's action is effectively prolonged.

The present disclosure provides improved methods for reprogramming and gene editing cells, including manufacturing a population of cells comprising cells of the lymphoid lineage and/or cells of the myeloid lineage.

Described herein are engineered proteins and methods of use of such proteins. Also described herein are complexes, compositions, and systems including engineered proteins of the present invention, each of which may be used for modifying and/or editing a target nucleic acid, such as to generate large deletions or inversions within the target nucleic acid.

The subject matter disclosed herein is generally directed to methods of treating a tumor capable of an epithelial-to-mesenchymal transition (an EMT cancer) by targeting the mesenchymal cell state. Disclosed are novel gene dependencies in the mesenchymal cell state. Also, disclosed are novel drugs that target the mesenchymal cell state.

The present disclosure provides compositions comprising engineered integration enzymes/eLSR and methods of using the same. In certain embodiments, the engineered integration enzyme comprises mutation(s) that substantially maintain or enhance integration activity at a pair of cognate integration recognition sites, and substantially decrease off-target integration activity at a pair of off-target integration recognition sites, when compared to a corresponding large serine integrase without said one or more substitutions (cLSR). The eLSR may further comprise a stabilization domain that increases the stability of the integration enzyme as compared to integration enzymes not comprising the stabilization domain.