The humanized mouse model is a powerful tool that excels in replicating human physiological and pathological characteristics, outshining traditional transgenic (Tg) animal models. This makes it the preferred choice for studying human diseases and assessing the safety and effectiveness of potential therapeutics. The enhanced alignment with human biology leads to more precise predictions of drug responses and disease mechanisms, potentially streamlining the translation from preclinical research to clinical applications.
Despite their popularity, common humanized models — including transgenic (Tg) mice, coding sequence (CDS), and single-exon humanized mice — fall short in achieving full human gene integration into the mouse genome. These current-generation models come with notable limitations such as random insertion, complex genetic backgrounds, and inadequate humanized regions.
To advance our understanding of disease mechanisms and drug development, there is a pressing need for full-length genomic DNA humanized mice. These models can faithfully replicate human gene expression patterns, regulations, and functional properties in a mouse model. However, replacing the entire genomic DNA sequence poses technical challenges as introducing large exogenous sequences may impact the expression and regulation of endogenous genes, presenting a significant obstacle.
In response to these demands, Cyagen has introduced the HUGO-GT™ (Humanized Genomic Ortholog for Gene Therapy) program. We employ our proprietary TurboKnockout-Pro technology to perform in-situ replacement of the targeted mouse endogenous gene, creating full-length genomic sequence humanized mouse models with a broader range of intervention targets.
Our HUGO-GT™ mice utilize highly efficient large-fragment vector fusion technology, serving as a versatile template for customized targeted mutagenesis. This approach allows us to provide clinically relevant humanized mouse models closely aligned with real-world biological mechanisms.
In addition to our mouse models, we offer Contract Research Organization (CRO) services in various fields, including ophthalmology, neuroscience, tumor immunology, and other disease areas. Our aim is to empower research on genetic diseases and facilitate the development of gene therapy drugs.
| Product Number | Product | Strain Background | Application |
|---|---|---|---|
| C001396 | B6J-hRHO | C57BL/6JCya | Retinitis Pigmentosa (RP), Congenital Stationary Night Blindness (CSNB), and other retinal diseases. |
| C001410 | B6-htau | C57BL/6JCya | Frontotemporal Dementia (FTD), Alzheimer's Disease (AD), and other neurodegenerative diseases. |
| C001418 | B6-hTARDBP | C57BL/6JCya | Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), and other neurodegenerative diseases. |
| C001427 | B6-hSNCA | C57BL/6NCya | Parkinson's Disease (PD). |
| C001437 | B6-hIGHMBP2 | C57BL/6NCya | Spinal Muscular Atrophy with Respiratory Distress Type 1 (SMARD1) and Charcot-Marie-Tooth Disease Type 2S (CMT2S). |
| C001495 | B6-hRHO-P23H | C57BL/6JCya | Retinitis pigmentosa (RP), congenital stationary night blindness (CSNB), and other retinal diseases research |
| C001504 | B6-hSMN2(SMA) | C57BL/6NCya | Spinal muscular atrophy (SMA) |
| I001128 | B6-hMECP2 | C57BL/6NCya | Rett Syndrome (RTT) |
| I001124 | B6-hLMNA | C57BL/6NCya | Hutchinson-Gilford Progeria Syndrome (HGPS) |
| C001398 | B6-hATXN3 | C57BL/6NCya | Spinocerebellar Ataxia Type 3 (SCA3) |
| C001512 | B6-hTTR | C57BL/6NCya | Transthyretin Amyloidosis (ATTR) |
| I001131 | B6-hSCN2A | C57BL/6NCya | Epilepsy |
| I001132 | B6-hCFTR | C57BL/6NCya | Cystic Fibrosis (CF) |
| C001525 | H11-Alb-hTTR*V50M | C57BL/6NCya | Transthyretin Amyloidosis (ATTR) |
| I001130 | B6-hATP7B | C57BL/6NCya | Hepatolenticular Degeneration (HLD) |
| Type | Disease | Target Gene | Target Type |
|---|---|---|---|
| Ophthalmology | Leber's congenital amaurosis 10 | CEP290 | Humanization (WT, Mut) |
| Age-Related Macular Degeneration (AMD) | VEGFA | Humanization | |
| ABCA4 | Humanization (WT, Mut) | ||
| Neurology | Amyotrophic lateral sclerosis (ALS) | SOD1 | Humanization |
| FUS | Humanization (WT, Mut) | ||
| Familial Dysautonomia (FD) | ELP1 | Humanization (WT, Mut) | |
| Myology/Muscle | Duchenne Muscular Dystrophy (DMD) | DMD | Humanization (WT, Mut, KO) |
| Spinal Muscular Atrophy (SMA) | SMN1 | Humanization | |
| Metabolism | Atherosclerosis (AS) | APOE2 | Humanization |
| APOE3 | Humanization | ||
| APOE4 | Humanization | ||
| Hematology/Blood | Hemophilia A (HA) | F8 | Humanization (WT, Mut) |
In the realm of gene therapy for conditions like Duchenne muscular dystrophy (DMD) and Retinitis pigmentosa (RP), numerous successful preclinical drug development cases have utilized humanized disease models. Cyagen's HUGO-GT™ model steps in to replace existing humanized models, catering to the research needs of pharmaceutical companies. It's especially beneficial for gene therapy drugs requiring stringent gene sequence integrity, such as ASO, CRISPR, and siRNA.
Our internal research team has validated that the humanized region of the HUGO-GT™ model mirrors the pathogenic genes in humans and encompasses most drug targets. Our CRO service team possesses a deep understanding of clinical drug targets, offering comprehensive project support to expedite the drug screening process.
Cyagen's proprietary TurboKnockout® technology and BAC fusion technology conquer the challenges of large-scale genomic segment replacement. This allows for complex model gene editing, achieving complete coverage of disease hotspot mutation regions, including exons, introns, and both UTR regions. HUGO-GT™ offers a superior degree of humanization compared to traditional models, meeting the needs of pharmaceutical companies and researchers without encountering patent or ownership disputes.