Genetic Engineering

Leveraging our knowledge and expertise in molecular biology, synthetic biology, structural biology, genetics, genomics and protein science as well as innovative genetic engineering technologies, we have developed a highly efficient pipeline to generate a broad variety of mutations in mice, leading to the development of valuable genetic models for mechanistic studies, preclinical testing, and drug discovery.

Complex Genetic Modeling

We employ CRISPR gene editing, synthetic biology, recombineering, Cre-lox and recombinase-mediated cassette exchange (RMCE) technologies to engineer sophisticated genetic models. These capabilities include conditional gene activation and inactivation, precise point mutations, reporter lines, multiplex knockouts, and targeted replacement of large gene fragments, such as genomic humanization.

A prime example of our advanced genetic modeling is the creation of the Singularity Sapiens mouse. This project involved targeted replacement of a 2.5MB mouse VDJ gene segment with a 1MB human counterpart. Accomplished following 9 rounds of consecutive engineering in mouse embryonic stem cells via CRISPR gene editing followed by sequential RMCE, this achievement exemplifies our expertise in complex genetic engineering.

Next Generation Genetics

Traditional mammalian genetics involves a lengthy process to achieve desired genetic modifications, including constructing targeting vectors, introducing mutations into embryonic stem cells, creating chimera mice, and extensive backcrossing. The entire cycle can take several months to years and demands substantial effort and resources.

Next-generation genetics, powered by CRISPR-Cas9 technology, drastically reduces the time, space, and effort needed to generate genetically modified animals. CRISPR- Cas9 allows for precise and efficient genome editing, enabling the production of homozygous animals within a single generation and eliminating the need for multiple rounds of breeding.

This innovation is particularly advantageous for creating knockout (KO) mouse cohorts on specific genetic backgrounds. For instance, knocking out a conserved target gene in the Singularity Sapiens mice, which traditionally would take years, can now be accomplished within a few months. Coupling CRISPR gene-editing with In Vitro Fertilization (IVF) technologies, mouse cohorts of desired genetic modifications can be rapidly produced for various applications.