A modified T cell comprising a functional exogenous receptor is provided. The functional exogenous receptor comprises: (a) an extracellular ligand binding domain, (b) a transmembrane domain, and (c) an intracellular signaling domain (ISD) comprising a chimeric signaling domain (CMSD), wherein the CMSD comprises a plurality of Immune-receptor Tyrosine-based Activation Motifs (ITAMs) optionally connected by one or more linkers. Further provided are vectors, methods of producing, pharmaceutical compositions, kits, and methods of treatment thereof.

The present disclosure provides proteins, nucleic acids, systems and methods for enhancing the synthesis of a protein.

Disclosed herein are chimeric antigen receptors (“CARs”) comprising an antigen binding site that recognizes citrullinated polypeptides. Citrullinated polypeptides, such as citrullinated vimentin, fibrinogen, and filaggrin, are expressed in the synovium of subjects with rheumatoid arthritis. Further disclosed are T cells, and in particular, Treg cells, that express these CARs. Administration of these CAR-T cells is useful in the treatment of rheumatoid arthritis as well as other diseases associated with citrullinated peptides.

This disclosure concerns compositions and methods for increasing the expression of a polynucleotide of interest. Some embodiments concern novel transactivation polypeptides and variants thereof that have been identified in plants, and methods of using the same. Particular embodiments concern the use of at least one DNA-binding polypeptide in a fusion protein to target at least one transactivation polypeptide or variant thereof to a specific binding site on a nucleic acid comprising the polynucleotide of interest, such that its expression may be increased.

The present disclosure provides drug responsive domains derived from human carbonic anhydrase 2 that can modulate protein stability for human interleukin 15 (EL15) payloads, as well as compositions and methods of use thereof.

The present invention provides a novel fusion polypeptide containing a catalytic domain of NPP1 fused to a targeting moiety, nucleic acids encoding the fusion polypeptide, a vector containing the nucleic acid integrated thereinto, a host cell transformed with the vector and pharmaceutical compositions comprising the fusion polypeptide.

The present disclosure relates to anti-glyco-CD44 antibodies and antigen binding fragments thereof that specifically bind to a cancer-specific glycosylation variant of CD44 and related fusion proteins and antibody-drug conjugates, as well as nucleic acids encoding such biomolecules. The present disclosure further relates to use of the antibodies, antigen-binding fragments, fusion proteins, antibody-drug conjugates and nucleic acids for cancer therapy.

The invention disclosed herein relates to improved methods for expanding cell populations, particularly B cell populations. The invention further relates to improved B-cell expansion media, compositions comprising expanded B cells and methods of using such expanded B cells. The invention further relates to methods of treating diseases or disorders wherein a population of B cells is obtained and cultured, and wherein said B cells are engineered to express a payload and/or a chimeric receptor, and wherein said B cells are administered to a subject.

Methods of producing recombinant, multi-component proteins in eukaryotic expression systems, comprising co-transforming a eukaryotic cell with two or more different nucleic acid constructs, each comprising a respective transcriptional unit encoding a protein component, wherein each nucleic acid construct comprises the same promoter and signal sequence, such that each of the components will be targeted to the same organelle of the cell for expression and intracellular assembly. In one or more embodiments, each nucleic acid construct comprises a promoter from a protein storage gene that is operably linked to a DNA sequence that encodes for a protein storage-specific signal sequence.

Disclosed herein include methods, compositions, and kits suitable for use in the delivery of polyribonucleotides and circuits. There are provided, in some embodiments, RNA exporter proteins comprising an RNA-binding domain, a membrane-binding domain, and an interaction domain capable of nucleating self-assembly. Disclosed herein include polynucleotides encoding cargo RNA molecule(s). In some embodiments, a plurality of RNA exporter proteins are capable of self-assembling into lipid-enveloped nanoparticles (LNs) secreted from a sender cell in which the RNA exporter proteins are expressed, thereby generating a population of LNs comprising a fusogen and exported cargo RNA molecule(s).