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.

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)
IR1019 SD-hGFAP Rat Sprague-Dawley Alexander disease (AxD), traumatic brain injury
C001533 B6-hINHBE C57BL/6NCya Obesity, metabolic disorders associated with improper fat distribution and storage
C001538 B6-hCOL7A1*c.6527dupC C57BL/6NCya Dystrophic Epidermolysis Bullosa (DEB)
C001428 B6-hCOL7A1 C57BL/6NCya Epidermolysis Bullosa (EB)

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

  1. In Situ Gene Replacement: Full genomic sequences (UTR, exon, intron) ensure accurate human gene function within the mouse genomic context and in vivo environment.
  2. Minimal Gene Regulation Disruption: Maintains natural regulation and expression patterns, preserving different isoforms across tissues and cell types.
  3. Flexible and Efficient: Initial wild-type humanization on mouse ES cells allows rapid introduction of disease-causing mutations, facilitating drug testing and research.
  4. Superior Accuracy: Reduces artifacts seen in other models, providing phenotypes that closely resemble human conditions.
  5. Comparative Superiority: Outperforms models with simple point mutations, CDS-only replacements, and BAC transgenes with random integration.