This disclosure provides, among other things, a transgenic animal that uses gene conversion for antibody diversification, comprising B cells in which the endogenous immunoglobulin heavy chain locus comprises: (a) a functional immunoglobulin heavy chain gene comprising a nucleic acid encoding an autonomous heavy chain (AHC) variable domain; and (b) a plurality of pseudogenes that are operably linked to said functional immunoglobulin heavy chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding the AHC variable domain of (a), wherein the pseudogenes are upstream or downstream of the functional immunoglobulin heavy chain gene.

This disclosure provides, among other things, a transgenic chicken. In some embodiments, the transgenic chicken comprises B cells in which the endogenous immunoglobulin heavy chain locus comprises: (a) a functional immunoglobulin heavy chain gene comprising a nucleic acid encoding a heavy chain variable domain in which the CDR3 is in the range of 30-60 amino acids in length and comprises at least 2 cysteine residues; and (b) a plurality of pseudogenes that are operably linked to said functional immunoglobulin heavy chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding the heavy chain variable domain of (a), wherein the pseudogenes are upstream or downstream of the functional immunoglobulin heavy chain gene.

Provided herein is a transgenic chicken comprising a genome having an endogenous immunoglobulin heavy chain gene in which the IgY CH1 coding sequence is functionally deleted. In certain embodiments, in B cells of the chicken the endogenous immunoglobulin heavy chain gene comprises: (a) a functional immunoglobulin heavy chain gene comprising, in operable linkage, a nucleic acid encoding an antibody heavy chain variable domain and a constant region coding sequence in which the IgY CH1 coding sequence is functionally deleted; and (b) a plurality of pseudogenes that are operably linked to said functional immunoglobulin heavy chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding the variable domain of (a), wherein the pseudogenes are upstream of the nucleic acid encoding an antibody heavy chain variable domain of (a).

This disclosure provides, among other things, a transgenic animal that uses gene conversion for antibody diversification comprising B cells in which the endogenous immunoglobulin heavy chain locus comprises: (a) a functional immunoglobulin heavy chain gene comprising a nucleic acid encoding a human heavy chain variable domain; and (b) a plurality of pseudogenes that are operably linked to the functional immunoglobulin heavy chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding the human heavy chain variable domain of (a), wherein the pseudogenes are upstream or downstream of the functional immunoglobulin heavy chain gene and encode variable domains that have camelizing amino acid substitutions.

Described herein are methods of producing transgenic Bombyx mori by targeting and modifying genomic regions associated with the heavy chain fibroin protein. Embodiments include insertion and truncation vectors utilized for modifying the FibH gene. Embodiments include plasmid constructs utilized for molecular cloning of donor sequences configured for replacement of or insertion into the FibH 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 an enhanced silk product with a high percentage of spider silk proteins. Embodiments include a silk product produced by such transgenic Bombyx mori.

The present invention provides compositions of recombinant human lysosomal acid lipase having particular glycosylation patterns for internalization into target cells, a vector containing the nucleic acid encoding human lysosomal acid lipase, a host cell transformed with the vector, pharmaceutical compositions comprising the recombinant human lysosomal acid lipase and method of treating conditions associated with lysosomal acid lipase deficiency.

Provided herein are methods and compositions related to non-human animals that express exogenous Terminal Deoxynucleotidyltransferase (TdT).

This disclosure provides, among other things, a transgenic animal and a method of using the same to make antibodies that have a common light chain. In certain embodiments, the transgenic animal may comprising a genome comprising a common light chain transgene, wherein the common light chain transgene comprises a non-immunoglobulin light-chain promoter and a common light-chain coding sequence. In certain embodiments, the common light chain is constitutively expressed.

This disclosure provides, among other things, strategies for minimizing antibody diversification in a transgenic animal that uses gene conversion for antibody diversification. In some embodiments, the animal may comprise a genome comprising an endogenous immunoglobulin light chain locus comprising: (a) a functional immunoglobulin light chain gene comprising a nucleic acid encoding a light chain variable region; and (b) a plurality of pseudogenes that are operably linked to the functional immunoglobulin light chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding a light chain variable region, wherein the pseudogenes are upstream or downstream of the functional immunoglobulin light chain gene and encode the same amino acid sequence as the light chain variable region of the functional immunoglobulin light chain gene of (a). In other embodiments, the locus may have a tandem array of coding sequences for the light chain.

Genetically modified mice and methods for making an using them are provided, wherein the mice comprise a replacement of all or substantially all immunoglobulin heavy chain V gene segments, D gene segments, and J gene segments with at least one light chain V gene segment and at least one light chain J gene segment. Mice that make binding proteins that comprise a light chain variable domain operably linked to a heavy chain constant region are provided. Binding proteins that contain an immunoglobulin light chain variable domain, including a somatically hypermutated light chain variable domain, fused with a heavy chain constant region, are provided. Modified cells, embryos, and mice that encode sequences for making the binding proteins are provided.