Herein is reported a transgenic vector comprising a humanized light chain locus, wherein said humanized light chain locus comprises (a) a V gene segment derived from human light chain V segment IGKV1-39-01, (b) 3′ proximal to said light chain gene segment a promoter, and (c) 5′ proximal to said light chain gene segment at least a fragment of the human IGKJ4 J-element.

A chimeric non-human mammal disease model, wherein (1) at least 30% of all the glial cells in the corpus callosum of the chimeric non-human mammal are human glial cells, and/or (2) at least 5% of all of the glial cells in the white matter of the brain and/or brain stem of the chimeric non-human mammal are human glial cells, and wherein the human glial cells comprise a combination of a first group of human glial cells tagged with a first label and a second group of human glial cells tagged with a second label that is distinguishable from the first label.

The invention discloses methods for the generation of chimaeric human—non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

Provided herein are methods and compositions related to the in vivo testing of therapeutic agents comprising a human Fc in genetically modified rodents (e.g., the testing of the pharmacokinetic and/or pharmacodynamic properties of such a therapeutic agent in genetically modified rodents). In some embodiments the genetically modified rodents express antibodies comprising a human Fc (e.g., a human IgG1 Fc, a human IgG4 Fc). In some embodiments, the rodents express fully human antibodies (i.e., antibodies having human heavy chains and human light (γ or κ) chains). In certain embodiments the genetically modified rodents comprise one or more Fc receptors with a human extracellular domain (e.g., a Neonatal Fc Receptor (FcRn), a β-2-microglobulin polypeptide (β2M), a Fc ε receptor 1 α (FcεR1α), a Fc γ receptor 1 alpha (FcγR1a), a Fc gamma receptor 2a (FcγR2a), a Fc gamma receptor 2b (FcγR2b), a Fc gamma receptor 3a (FcγR3a), a Fc gamma receptor 3b (FcγR3b), a Fc gamma receptor 2c (FcγR2c)). The transmembrane and cytoplasmic domain of such receptors can be human or non-human (e.g., rodent).

The present disclosure encompasses engineered meganucleases that bind and cleave recognition sequences within a dystrophin gene. The present disclosure also encompasses methods of using such engineered meganucleases to make genetically modified cells. Further, the disclosure encompasses pharmaceutical compositions comprising engineered meganuclease proteins, or polynucleotides encoding engineered meganucleases of the disclosure, and the use of such compositions for the modification of a dystrophin gene in a subject, or for treatment of Duchenne Muscular Dystrophy.

The present invention provides an anti-IGF-I receptor antibody that binds specifically to an IGF-I receptor of a vertebrate and has the proliferation-inducing activity of a vertebrate-derived cell, or a fragment thereof, or derivatives of these.

Described are transgenic, non-human animals comprising a nucleic acid encoding an immunoglobulin light chain, whereby the immunoglobulin light chain is human, human-like, or humanized. The nucleic acid is provided with a means that renders it resistant to DNA rearrangements and/or somatic hypermutations. In one embodiment, the nucleic acid comprises an expression cassette for the expression of a desired molecule in cells during a certain stage of development in cells developing into mature B cells. Further provided is methods for producing an immunoglobulin from the transgenic, non-human animal.

Mice, tissues, cells, and genetic material are provided that comprise a humanized heavy chain immunoglobulin locus, a humanized light chain locus that expresses a universal light chain, and a gene encoding an ADAM6 or ortholog or homolog or functional fragment thereof. Mice are provided that express humanized heavy chains comprising human variable domains, and that express humanized light chains comprising human variable domains wherein the light chains are derived from no more than one, or no more than two, light chain V and J or rearranged V/J sequences. Fertile male mice that express antibodies with universal light chains and humanized heavy chains are provided. Methods and compositions for making bispecific binding proteins are provided.

The present invention provides cells, transgenic animals, including transgenic mammals and particularly rodents comprising engineered immunoglobulin (Ig) alleles. Such engineered alleles, wherein an Ig light chain CL exon [Cκ or Cλ (Cλ1, Cλ2 or Cλ3)] is incorporated into the Ig heavy chain locus, are capable of producing heavy chain-only antibodies as a single chain VH antibody (scVHAb) or heavy chain antibody (HCAb) comprising two extended scVHAbs. The scVHAb comprises an antigen-binding part consisting of a VH domain and the immunoglobulin constant domains CL, which is either Cκ or Cλ, and CH1, in the order from N-terminus to C-terminus: VH-L1-CL-L2-CH1, wherein L1 and L2 are each, independently, peptidic linkers; and wherein CL is paired with CH1 through beta-sheet contact thereby obtaining a CL/CH1 dimer.

The present disclosure relates to the genetically modified non-human animals that express a human or chimeric TIGIT (e.g., humanized TIGIT), and methods of use thereof.