Genetically engineered humanized mouse models for preclinical antibody studies

Abstract

The use of genetic engineering has vastly improved our capabilities to create animal models relevant in preclinical research. With the recent advances in gene-editing technologies, it is now possible to very rapidly create highly tunable mouse models as needs arise. Here, we provide an overview of genetic engineering methods, as well as the development of humanized neonatal Fc receptor (FcRn) models and their use for monoclonal antibody in vivo studies.

Fig. 1

Process for creating transgenic mice, by injection of DNA, RNA, or oligonucleotides into the pronuclei or cytoplasm of fertilized oocytes. This process can be used for random transgenics, ZFN, TALEN, or CRISPR. CRISPR Clustered Regularly Interspaced Short Palindromic Repeats, TALEN transcription activator-like effector nucleases, ZFN zinc finger nucleases

Fig. 2

Process for creating mice via the ES cell route, by injecting ES cells into blastocysts. ES embryonic stem