The present application provides genetically modified non-human animals and methods for producing heavy chain-only antibodies (HcAbs), wherein the genetically modified non-human animal comprises a germline genome comprising an engineered immunoglobulin heavy chain (IgH) allele at an endogenous IgH locus, wherein the engineered IgH allele lacks functional gene segments encoding CH1 domains of all endogenous IgG subclasses. In some embodiments, a genetically modified mouse is provided, comprising an engineered IgH allele that lacks a functional endogenous gene segment encoding Cγ3, Cγ1, Cγ2b and CH1 exon of Cγ2c. Further provided are HcAbs or derivatives thereof produced by the genetically modified non-human animals.

Factor IX proteins are described with an increase in the number of glycosylation sites and other modifications to provide Factor IX proteins that have higher specific activity and a longer useful clotting function relative to wild type or non-modified Factor IX protein.

Genetically modified cells, tissues, and organs for treating or preventing diseases are disclosed. Also disclosed are methods of making the genetically modified cells and non-human animals.

This disclosure is directed to split intein protein production systems using transgenic target organisms such as Bombyx mori. A vector set for transforming a target organism includes: a first vector having a first donor sequence that encodes (i) a first non-native protein and (ii) at least one split intein domain; a second vector having a second donor sequence that encodes (i) a second non-native protein and (ii) at least one split intein domain. The respective split intein domains encoded by the first and second vectors are configured to associate with one another and ligate the first and second non-native proteins to thereby form a fused protein.

Described herein are methods of producing transgenic Bombyx mori by targeting and modifying genomic regions associated with sericin proteins. Embodiments include vectors utilized for modifying one or more sericin genes. Embodiments include plasmid constructs utilized for molecular cloning of donor sequences configured for replacement of or insertion into a targeted sericin gene and utilized for transfection of Bombyx mori with the donor sequences. Embodiments include transgenic Bombyx mori that have been transfected with the donor sequences and are capable of producing a non-native protein product with minimized or prevented production of sericin.

Disclosed are methods, compositions, and systems for transforming silkworms to produce spider silk and analogs of spider silk. In certain embodiments, the method may include inserting a DNA sequence coding for at least a portion of a spider silk fibroin polypeptide, or an analog of a spider silk fibroin polypeptide, positioned between at least a portion of the 5′ and 3′ ends of a silkworm fibroin gene to generate a fusion gene construct having a sequence that encodes for a polypeptide comprising both spider silk fibroin and silkworm silk fibroin sequences. In certain embodiments, the fused gene is able to replace a native gene present in the silkworm such that the transformed silkworm expresses a polypeptide comprising a spider silk fibroin polypeptide, or an analog thereof, and expresses significantly less of the native silkworm silk.

Provided herein are transgenic non-human animals whose genomes comprise two or more human genes selected from CD33, Siglec-5, Siglec-7, Siglec-9, Siglec-11, Siglec-14, and Siglec-16, to methods of screening candidate agents that bind to and/or modulate the function and/or activity of at least one of the human genes in the transgenic non-human animals, and to methods of screening candidate agents to determine their effect on one or more activities and/or functions associated with expression of at least one of the human genes in the transgenic non-human animals. Further provided herein are methods of recapitulating a human Siglec immune system in a non-human animal, and methods of generating a non-human animal disease model comprising a human Siglec repertoire.

A transgenic cloned piglet expressing human proinsulin and a method of preparing the same, and more particularly, to a recombinant vector for human proinsulin expression, a genetically modified cell line into which the recombinant vector is introduced, a transgenic cloned piglet expressing human proinsulin, and a method of producing the same.

A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that present a choice of two human light chain variable gene segments such that the immunoglobulin light chains expresses by the mouse comprise one of the two human light chain variable gene segments. Methods for making bispecific antibodies having universal light chains using mice as described herein, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, and host cells are provided.

A method for preparing a fish skin mucous gland bioreactor and its application, including: identifying genes specifically expressed in fish skin mucinous gland cells, promoters and secreted protein signal peptides, constructing transgenic expression vectors that can specifically express endogenous or heterologous biologically active substances in fish skin and mucous gland cells, developing stable genetic and transgenic fish that secrete bioactive substances into fish mucus, and using bioactive substances secreted by mucus glands for animal and plant growth, stress resistance and disease resistance, human health care and disease prevention, and commercial enzymes. The fish skin mucous gland bioreactor developed by the invention has the characteristics of easy breeding and expansion, more skin mucus secretion, convenient mucus collection, and easy purification of bioactive substances, and can realize the large-scale production of fish skin mucous gland bioreactor and efficient application.