FIELD: biotechnology.
SUBSTANCE: rodents are designed to produce antibodies that contain a light chain of immunoglobulin with a human variable domain, in which the amino acid histidine is encoded by a substituted or inserted germline codon. To obtain such rodents, a modification of its embryonic genome is performed to remove or reduce the endogenous V and J segments of the light chain of immunoglobulin to a non-functional state. Thereafter, a single rearranged human immunoglobulin light chain variable region gene sequence is inserted into the genome of said rodent, comprising sequences of VL and JL human, and the gene sequence of the immunoglobulin light chain constant region operably linked to a single rearranged human immunoglobulin light chain variable region gene sequence. The immunoglobulin light chain is capable of forming a pair with a number of heavy chains of immunoglobulin selected from the rodent. Each of the plurality of heavy chains of immunoglobulin specifically binds to different epitopes.
EFFECT: invention makes it possible to obtain antibodies having more efficient recycling, to prevent antibody degradation by promoting the dissociation of antibody-antigen complexes in the endosomal compartment without reducing the specificity and affinity of the antibody to the antigen.
47 cl, 14 dwg, 6 tbl, 5 ex
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Authors
Dates
2018-02-13—Published
2013-03-15—Filed