Production of humanized antibodies in transgenic animals

摘要

Disclosed are humanized immunoglobins prepared from transgenic non-human animals. The animals are genetically altered to comprise a humanized Ig locus that is capable of undergoing gene conversion and producing a repertoire of humanized immunoglobins in the animal. Also disclosed are recombinant vectors for replacing an Ig gene segment from an animal which relies primarily on gene conversion in generating antibody diversity, such as rabbit, pig, chicken, sheep or cow, with a human Ig gene segment. The vector comprises a 5' nucleotide sequence, the human Ig gene segment and a 3' nucleotide segment, wherein the 5' and 3' nucleotide sequences are homologous to the 5' and 3' flanking sequences of the Ig gene segment from the animal.