However, most commonly used humanized models, such as transgenic (Tg) mice, coding sequence (CDS), and single-exon humanized mice, can only achieve partial insertion of the human gene into the mouse genome. These common, current-generation, humanized models exhibit notable limitations, including random insertion, complex genetic background and line establishment, as well as inadequate humanized regions.
To facilitate further advancement of disease mechanistic study and related drug development, full-length genomic DNA humanized mice which can faithfully recapitulate the expression pattern, regulation, and functional properties of the human gene in a mouse model, is urgently needed to replace the existing animal models and reshape the translational research framework for drug development. However, achieving entire genomic DNA sequence replacement poses technical challenges, as the large-scale introduction of exogenous sequences may affect the expression and regulation of endogenous genes, which brings a very daunting problem.
Driven by above demands, Cyagen has launched the HUGO-GT™ (Humanized Genomic Ortholog for Gene Therapy) program. We use our proprietary TurboKnockout-Pro technology to achieve in-situ replacement of the targeted mouse endogenous gene and successfully construct full-length genomic sequence humanized mouse models that encompass a broader range of intervention targets.
The HUGO-GT™ mice employ more efficient large-fragment vector fusion technology, which serves as a versatile template for targeted mutagenesis customization services, providing clinically relevant models that are closely aligned to real-world biological mechanisms.
Additionally, we offer CRO services in fields including ophthalmology, neuroscience, tumor immunology, and other disease areas, to empower research on genetic diseases and facilitate the development of gene therapy drugs.
and technology commercialization
Licensing of whole genomic DNA humanized models
Novel drug development
Other flexible collaboration options
The rhodopsin protein encoded by the human RHO gene is necessary for normal vision, and is critical for the transmission of low-light signals. Mutations in the RHO gene have been identified as associated with ophthalmic diseases such as retinitis pigmentosa (RP) and congenital stationary night blindness (CSNB). Currently, gene therapies targeting RHO, such as ASO and CRISPR, are being developed. The application of the HUGO-GT™ whole genomic DNA humanized animal model will help advance potential RHO-related therapies towards clinical trials.
Cyagen utilized embryonic stem (ES) cell gene editing and targeting technology to replace a 500bp fragment downstream of the Rho gene ATG promoter in C57BL/6J mice with a 500bp fragment downstream of the human RHO gene ATG promoter, thus creating the B6-hRHO mouse. Based on this, we further constructed the B6-hRHO (P23H) mouse model with a hot-spot mutation.
The results here indicated that the RHO protein encoded by the human gene was expressed normally in the B6-hRHO mouse, and its retinal morphology and function were similar to those of the wild-type mouse, showing no visual defects. However, the B6-hRHO (P23H) mutation mouse exhibited a phenotype of retinitis pigmentosa. These data demonstrated the successful construction of B6-hRHO and B6-hRHO (P23H) models, which can be used to study the pathogenic mechanisms of retinitis pigmentosa and the development of related new drugs.