Our Technology​

The optimization of HIS (Human Immune System) mouse models requires diverse genetic modifications, including gene knockout, knock-in, and transgenic overexpression of specific genes. However, the germline potency of embryonic stem cells (ESCs) derived from NOG/NSG mice is not well-suited for direct genetic editing, posing a significant challenge.

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Currently, the most widely used approach involves creating transgenic or knock-in mice for each human gene of interest on the C57BL/6 background, followed by backcrossing onto the NSG/NOG background for at least ten generations. This process is extremely expensive, labor-intensive, and time-consuming, limiting its practicality for large-scale applications.

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Alternative strategies, such as the in vivo injection of recombinant proteins and hydrodynamic injection of plasmid DNA, offer promising avenues for HIS mouse model optimization. However, these gene delivery methods often result in transient, systemic, and supra-physiological protein expression, which can introduce artifactual effects. For long-term humanization studies, transgenic mice with stable and consistent cytokine expression are generally preferred over transient expression models.

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Since 2019, Genomab Biotech has been at the forefront of developing the next generation of HIS mouse models using a sophisticated DNA Microinjection Technique, focusing on the NOD/SCID genetic background. To date, we have successfully achieved murine gene disruption via CRISPR/Cas9-based knockout, humanization of mouse genes via CRISPR/Cas9-based knock-in, and overexpression of human genes through advanced pronuclear microinjection. These advancements represent significant progress toward creating more robust and physiologically relevant HIS mouse models.

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Additionally, we offer customized mouse model development services based on our state-of-the-art immune-deficient mouse models, tailored to meet specific research needs.