HUGO-GT™ Next-Generation Humanized Models

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.

Full-Length Genomic Sequence Humanized HUGO Mouse Models

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.

Validated Next-Generation Humanized Mouse Models

Product Number Product Strain Background Application
C001396 B6J-hRHO C57BL/6J Retinitis Pigmentosa (RP), Congenital Stationary Night Blindness (CSNB), and other retinal diseases.
C001410 B6-htau C57BL/6J Frontotemporal Dementia (FTD), Alzheimer's Disease (AD), and other neurodegenerative diseases.
C001418 B6-hTARDBP C57BL/6J Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), and other neurodegenerative diseases.
C001427 B6-hSNCA C57BL/6N Parkinson's Disease (PD).
C001428 B6-hCOL7A1 C57BL/6N Epidermolysis Bullosa (EB).
C001437 B6-hIGHMBP2 C57BL/6N Spinal Muscular Atrophy with Respiratory Distress Type 1 (SMARD1) and Charcot-Marie-Tooth Disease Type 2S (CMT2S).
C001495 B6-hRHO-P23H C57BL/6J Retinitis pigmentosa (RP), congenital stationary night blindness (CSNB), and other retinal diseases research
C001504 B6-hSMN2(SMA) C57BL/6N Spinal muscular atrophy (SMA)
I001128 B6-hMECP2 C57BL/6N Rett Syndrome (RTT)
I001124 B6-hLMNA C57BL/6N Hutchinson-Gilford Progeria Syndrome (HGPS)
C001398 B6-hATXN3 C57BL/6N Spinocerebellar Ataxia Type 3 (SCA3)
C001512 B6-hTTR C57BL/6N Transthyretin Amyloidosis (ATTR)
I001131 B6-hSCN2A C57BL/6N Epilepsy
I001132 B6-hCFTR C57BL/6N Cystic Fibrosis (CF)

Upcoming Next-Generation Humanized Mouse Models

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)

Advantages of HUGO-GT™ Genomic DNA Humanized Model

Versatile Tool for Preclinical Drug Experiments

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.

Efficient Drug Screening

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.

Full-length Coverage of Pathogenic Genes

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.

Tailored Customization

Leveraging extensive project experience, Cyagen's R&D team offers efficient whole genomic DNA humanized customization services for HUGO-GT™ model development. Not only can we perform custom site-specific targeting of large gene segments up to 350 Kb, but we can also re-modify existing HUGO-GT™ wild-type humanized ES cells, facilitating the rapid creation of disease models. This results in shorter construction times and higher success rates, providing experimental animal models and littermate controls for preclinical research purposes.