Our Technology​

The optimization of HIS mouse models requires different genetic modifications, including the knockout, knock-in, and transgenic overexpression of specific genes. However, the germ line potency of embryonic stem cells (ESCs) derived from NOG/NSG mice is not favorable to direct genetic editing.

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The most popular current approach to generating transgenic or knock-in NSG/NOG mice entails the creation of transgenic or knock-in mice for each human gene of interest one at a time on the C57BL/6 background, followed by backcrossing onto the NSG/NOG background for at least ten generations, which is an extremely expensive, laborious, and time consuming process.

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The in vivo injection of recombinant proteins, the hydrodynamic injection of plasmid DNA, and the use of adeno-associated viruses represent promising alternative approaches to HIS mouse model optimization. These gene delivery strategies, however, result in transient, systemic, and generally supra-physiological protein expression and can therefore potentially yield artifactual effects. For longer term humanization experiments, the use transgenic mice with consistent cytokine expression is thus often preferred over transient expression models.

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Since 2019, Genomab Biotech has been dedicated to developing the next generation of HIS mouse models using a sophisticated DNA Microinjection Technique, with a particular focus on the NOD/SCID genetic background. To date, we have been able to disrupt murine genes via a CRISPR/Cas9-based knockout approach, achieve the humanization of mouse genes via a CRISPR/Cas9-based knock-in approach, and overexpress human genes by advanced pronuclear microinjection.