In Vivo Model Development for Hemophilia

Protheragen offers a comprehensive in vivo animal model development service tailored for hemophilia research and drug development. Leveraging a wide array of validated species, genetic backgrounds, and induction methodologies, our platform is designed to support preclinical efficacy, safety, and mechanistic studies of novel hemophilia therapeutics.

Hemophilia is a group of inherited bleeding disorders characterized by deficiencies in coagulation factors, most commonly factor VIII (hemophilia A) or factor IX (hemophilia B). Robust animal models are essential for elucidating disease mechanisms, evaluating therapeutic candidates, and predicting clinical outcomes. At Protheragen, we utilize a diverse selection of species—including mice (Mus musculus), rats (Rattus norvegicus), rabbits (Oryctolagus cuniculus), and non-human primates (Macaca fascicularis)—across a broad range of genetic strains and backgrounds. Our portfolio includes knockout, transgenic, chemically-induced, and antibody-induced models that closely recapitulate the pathophysiology and clinical features of human hemophilia, ensuring translational relevance and high-quality data for our clients.

Genetic Knockout Models

Genetic knockout models are established by targeted disruption of coagulation factor genes, such as F8 (factor VIII), F9 (factor IX), or other related genes, in mice and rats. These models are developed using homologous recombination or CRISPR/Cas9-mediated gene editing. They exhibit spontaneous or injury-induced bleeding phenotypes, mirroring the clinical manifestations of hemophilia A or B. Advantages include precise genetic control, reproducibility, and the ability to study gene-gene or gene-environment interactions. Primary applications include efficacy testing of gene therapies, recombinant proteins, and cell-based treatments, as well as mechanistic studies of coagulation and immune tolerance.

Chemically-Induced Models

Chemically-induced models involve the administration of anticoagulant agents (such as apixaban, dabigatran, or rivaroxaban) to wild-type animals, often combined with standardized injury protocols (e.g., tail vein clipping or transection). These models produce transient coagulopathies and controlled bleeding episodes, allowing for rapid screening of hemostatic agents and reversal strategies. Key advantages include flexibility, ease of induction, and suitability for high-throughput studies. They are primarily used for evaluating acute efficacy of novel therapeutics, pharmacokinetics, and drug-drug interactions.

Antibody-Induced Models

Antibody-induced models are generated by administering neutralizing antibodies against coagulation factors (e.g., anti-factor VIII antibodies) to animals, including mice, rabbits, and non-human primates. This approach mimics acquired hemophilia or inhibitor development seen in patients undergoing replacement therapy. These models are valuable for testing bypassing agents, immune tolerance induction strategies, and next-generation biologics. The main advantages are the ability to model inhibitor-positive hemophilia and the use of larger animal species for translational studies.

Transgenic and Xenograft Models

Transgenic models express human or modified coagulation factors, or carry additional gene modifications (such as F3, F9, F10, or antigen genes), while xenograft models involve engraftment of human hematopoietic stem cells into immunodeficient mice. These advanced models enable detailed studies of gene therapy vectors, immune responses to human proteins, and cell-based therapies in a physiologically relevant context. Their advantages include the ability to evaluate human-specific therapeutics and immunogenicity, making them ideal for translational research and preclinical validation.

Protheragen delivers a full-spectrum solution for hemophilia animal model studies, from model selection and development to comprehensive in vivo efficacy and safety evaluation. Our service includes custom genetic engineering, chemical or antibody induction, surgical procedures (e.g., tail vein transection, saphenous vein incision), and advanced transgenic or xenograft model generation. Key efficacy endpoints include bleeding time, blood loss quantification, survival analysis, coagulation assays (aPTT, PT), inhibitor titers, and tissue histopathology. Analytical capabilities encompass ELISA, flow cytometry, molecular genotyping, gene/protein expression profiling, and in vivo imaging. All studies are conducted under rigorous quality control protocols, with validated SOPs, ethical compliance, and detailed data reporting to ensure reproducibility and regulatory acceptance.

Partnering with Protheragen provides access to a robust, scientifically validated platform for hemophilia model development and preclinical testing. Our experienced team ensures tailored study design, expert technical support, and timely delivery of high-quality data, accelerating your therapeutic pipeline from discovery to clinical translation. Contact us today to discuss your hemophilia research needs or to request a customized project proposal.