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HomePreclinical Mouse ModelsHumanized Target Gene Disease Models

CDS-Humanized Target Gene Mouse Models

Cyagen develops CDS-humanized mouse models by replacing endogenous mouse coding sequences with human CDS regions under native mouse regulation. Test clinical antibodies, ADCs and small molecules against the true human target, enabling more relevant target validation and efficacy studies while accelerating preclinical research and therapeutic development.
Flexible Humanization
Humanize selected coding regions or the full CDS based on therapeutic binding sites, protein function, and study requirements.
Accelerated Model Development
Humanize a single exon, a functional domain or the full CDS, with up to 50% faster model delivery than conventional methods.
Target-Specific Validation Data
Test oncology, immunotherapy and hematologic drugs in pre-validated CDS-humanized models with clinically relevant drug responses.
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FAQs
Overview

What Is a CDS-Humanized Mouse Model?

CDS-humanized mouse models are genetically engineered to express fully or partially humanized target proteins. Depending on the design, selected mouse coding regions are replaced or modified using corresponding human sequences. Regulatory elements and expression patterns vary by model and should be evaluated using target-specific validation data.
This approach can be particularly useful for therapeutics that recognize human-specific protein regions, for example an antibody that recognizes a human-specific epitope, or a small molecule that binds a pocket that differs between species. It enables studies with the clinical candidate rather than a mouse-reactive surrogate, improving the translational value of preclinical data.

CDS Humanization vs. Full-Gene Humanization (HUGO-GT™): Which Do You Need?


Cyagen offers two complementary target-humanization strategies. The right choice depends on how your therapeutic engages the target.

CDS-Humanized Mice


Only the coding sequence is humanized (the full CDS, selected exons or a functional domain), while the mouse promoter and UTRs are retained. This is the efficient choice for drugs that act on the protein: antibodies, ADCs, bispecifics, fusion proteins, small molecules and cell therapies. Key question answered: does my drug bind and act on the human protein in vivo?

HUGO-GT™ Full-Gene Humanized Mice


The full-length human gene is introduced, including introns and, in many models, the 5′ and 3′ UTRs, supporting human splicing and RNA-level regulation. This is required for drugs that act on human DNA or RNA sequences: ASOs, siRNAs, splice-switching drugs, base or prime editing, and AAV/LNP gene therapies.
Learn more about HUGO-GT™ humanized mice.

Rule of thumb: CDS humanization is often suitable when the study primarily requires a humanized protein target. Full-gene humanization may be preferable when therapeutic activity depends on human-specific genomic sequences, transcript structures, or regulatory elements. The optimal strategy should be determined by the therapeutic mechanism of action and the required experimental endpoints.
Explore Ready-to-Use Mouse Models
Discover over 18,000 validated mouse strains—including knockout, conditional knockout, and humanized models—covering 20+ research areas such as oncology, neurology, and metabolism. All models are supported by detailed genotype data and guaranteed quality, helping you fast-track discovery with confidence.
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Catalog NumberNameBase StrainResearch ApplicationAction
C001339Alb-Cre+/hMYC-IRES-EGFP+C57BL/6JCyaLiver Cancer Research: The model overexpresses the MYC oncogene in the liver, spontaneously developing liver cancer, thus serving as a tool to study the mechanisms of liver cancer initiation and progression. Drug Screening and Evaluation: Utilized to assess the efficacy of new anti-liver cancer drugs and therapeutic strategies, particularly those targeting MYC-driven tumors. Gene Function Studies: Investigates the role of the MYC gene in hepatocytes and its involvement in tumor formation. Transcriptional Regulation Studies: Explores the mechanisms of MYC in transcriptional regulation and its interactions with other genes and signaling pathways.
C001793Cd11b-hCD89(FCAR)C57BL/6NCyaResearch on immune responses and autoimmune mechanisms; IgA nephropathy (IgAN) model establishment and drug efficacy evaluation; Preclinical evaluation of CD89-targeted therapies; Research on tumors and infectious diseases.
C002124hAPP-NL-FC57BL/6CyaResearch on Alzheimer's disease (AD); Research on Cerebral Amyloid Angiopathy (CAA); Preclinical research such as the development, screening, and efficacy evaluation of APP-targeted therapeutic drugs.
C002123hAPPC57BL/6CyaResearch on Alzheimer's disease (AD); Research on Cerebral Amyloid Angiopathy (CAA); Preclinical research such as the development, screening, and efficacy evaluation of APP-targeted therapeutic drugs.
I001137H11-hB2M&HLA-A24C57BL/6NCyaResearch on human viral infectious diseases; Development and testing of novel viral vaccines; Safety and immunogenicity testing of drugs and vaccines; Research on oncology and autoimmune diseases; Study of the interactions between human immune cells and pathogens; Research on homologous tumor transplantation (Syngeneic).
I001138H11-hB2M&HLA-A2.1C57BL/6NCyaResearch on human viral infectious diseases; Development and testing of novel viral vaccines; Safety and immunogenicity testing of drugs and vaccines; Research on oncology and autoimmune diseases; Study of the interactions between human immune cells and pathogens; Research on homologous tumor transplantation (Syngeneic).
C002105hSCN9AC57BL/6NCyaAnalgesic Drug Screening: Used to evaluate the potential analgesic effects and safety of therapeutic strategies targeting human Nav1.7, including small-molecule inhibitors, antisense oligonucleotides/PNA approaches, and gene therapies; Mechanistic Studies of Inherited Erythromelalgia (IEM): Used to investigate the mechanisms associated with gain-of-function variants of human Nav1.7 in inherited erythromelalgia (IEM) and to explore potential therapeutic strategies; Congenital Insensitivity to Pain (CIP) Studies: Used to investigate the mechanisms associated with loss-of-function variants of human Nav1.7 in congenital insensitivity to pain (CIP), as well as the molecular mechanisms underlying impaired pain signal transmission; Small Fiber Neuropathy (SFN) Studies: Used to investigate the pathological mechanisms of SCN9A variant-associated small fiber neuropathy (SFN) and to explore potential therapeutic targets.
C002068H11-hKLK2/hKLK3C57BL/6NCyaScreening, development, and evaluation of KLK2/KLK3-targeted drugs and immunotherapy strategies; Development and evaluation of immunotherapy strategies for prostate cancer (PCa).
C001338H11-CAG-LSL-hMYC-IRES-EGFPC57BL/6JCyaThe model can be mated with different tissue-specific Cre mice for the study of tumors in different tissues or organs.
C001226hACE2-EGFPC57BL/6NCyaCardiovascular function research; SARS-CoV-2 infection mechanism research; SARS-CoV-2 vaccine development evaluation; SARS-CoV-2 prevention and treatment drug screening evaluation; SARS-CoV-2 antibody drug development validation.
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FAQs

Frequently Asked Questions (FAQs)

What types of therapeutic research can benefit from CDS-humanized mice?

CDS-humanized mice can support therapeutic research in oncology, immunology, inflammation, neuroscience, metabolic and cardiovascular diseases, and rare diseases. Relevant modalities include monoclonal antibodies, bispecific and multispecific antibodies, antibody-drug conjugates (ADCs), antibody-oligonucleotide conjugates (AOCs), and small molecules targeting human proteins. They may also support siRNA and antisense oligonucleotide (ASO) studies when the humanized sequence includes the drug's target site. Suitability depends on the model's design, target expression, disease relevance, and the candidate's mechanism of action.

Why are humanized target models important for preclinical drug development?

Many antibodies, biologics and targeted small molecules are designed to recognize human proteins and may not bind the corresponding mouse targets. Humanized target mouse models can help address species-specific differences in therapeutic target recognition. When appropriately designed and validated, they provide an in vivo platform for evaluating target engagement and selected pharmacological responses using human-targeted therapeutic candidates.

Can a specific exon or protein domain be humanized instead of the entire CDS?

Yes. Humanization may cover a specific exon, a functional domain (such as the extracellular, drug-binding domain), multiple coding exons or the complete coding sequence. The strategy should consider protein structure, therapeutic binding sites, endogenous gene regulation and the biological functions that must be preserved.

Is the mouse gene still expressed in a CDS-humanized mouse?

Expression of the endogenous mouse protein depends on the humanization strategy and genotype. Some models express a fully humanized target protein, while others express a mouse-human chimeric protein. Homozygous and heterozygous animals may also differ in their target expression profiles. The exact design and validation data should be reviewed for each strain.

How do I select the right target gene humanized mouse model?

Base your selection on the therapeutic modality, the human-specific binding region, the disease indication, the required genetic background and your planned endpoints. Confirm the humanized sequence, protein expression, tissue distribution and available validation data before starting. Our scientists can recommend CDS or HUGO-GT™ full-gene humanization for your program.
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