A transgenic non-human animal is provided. In certain embodiments, the animal comprises a genome comprising an immunoglobulin heavy chain locus comprising: a) a transcribed gene encoding a fusion protein comprising, from N-terminus to C-terminus: i. a scaffold comprising a first binding domain; and ii. a heavy chain constant region operably linked to the scaffold; wherein the scaffold is capable of specifically binding to a target in the absence of additional polypeptides; and b) a plurality of pseudogenes that are operably linked to the transcribed gene and that donate, by gene conversion, nucleotide sequence to the part of the transcribed gene that encodes the binding domain.

Provided herein are compositions and methods to identify a binding element (e.g., peptide, peptoid, or protein) that can be bound by an immunoreceptor (e.g., antibody). The binding element can be provided in a target binding unit comprising two binding elements separated by a spacer such that the two binding elements simultaneously bind to a single molecule comprising an antigen binding domain of an antibody. The present disclosure provides various methods to construct the spacer. The identified binding elements can be further used to manufacture an array which can be used to profile antibodies obtained from a blood sample.

Disclosed is a method for improving affinity of an antibody for an antigen, comprising, in an unmodified antibody, improving affinity for an antigen as compared to the unmodified antibody, by changing 17th, 18th and 20th amino acid residues of a light chain defined by Kabat method to charged amino acid residues.

The present invention provides synthetic canine antibody libraries, as well as polypeptides, nucleic acids, vectors, host cells and methods used in conjunction with these libraries. The present invention also provides antibodies isolated from such libraries.

The method involves an approach of inhibiting replication of dysfunctional cells which adopt alternative lengthening of telomeres, or “ALT.” The methodology involves inhibition of Fanconi anemia complementation group M (FANCM), and one or both of breast cancer 1 (BRCA1) and Bloom syndrome protein (BLM). These molecules are the keys to the elimination of replication stress caused by ALT. In other words, they permit the dysfunctional cells to proliferate. Inhibition of these molecules inhibits proliferation.

The method involves an approach of inhibiting replication of dysfunctional cells which adopt alternative lengthening of telomeres, or “ALT.” The methodology involves inhibition of Fanconi anemia complementation group M (FANCM), and one or both of breast cancer 1 (BRCA1) and Bloom syndrome protein (BLM). These molecules are the keys to the elimination of replication stress caused by ALT. In other words, they permit the dysfunctional cells to proliferate. Inhibition of these molecules inhibits proliferation.

Anti-PVRIG and anti-TIGIT antibodies are provided.

Disclosed are antigen binding polypeptides and antigen binding polypeptide complexes (e.g., antibodies and antigen binding fragments thereof) having certain structural features. Also disclosed are polynucleotides and vectors encoding such polypeptides and polypeptide complexes; host cells; chimeric antigen receptors (CARs); immune cells; pharmaceutical compositions and kits containing such polypeptides and polypeptide complexes; and methods of using such polypeptides and polypeptide complexes.

A method for creating a plasmid for use in producing a chimeric antibody, comprising (a) receiving a FAB region of the antibody; (b) receiving a fluorescent protein; (c) receiving a linker having length of at least 5 amino acids; (d) using the Gibson assembly process to join the FAB region, the fluorescent protein, and the linker into an expression plasmid.

A method for creating a plasmid for use in producing a chimeric antibody, comprising (a) receiving a FAB region of the antibody; (b) receiving a fluorescent protein; (c) receiving a linker having length of at least 5 amino acids; (d) using the Gibson assembly process to join the FAB region, the fluorescent protein, and the linker into an expression plasmid.