Drug Screening in Animal Models    

Service Content

Creative Biogene offers a comprehensive animal model efficacy assessment service, aiding in understanding the pharmacokinetics, pharmacodynamics, and therapeutic potentials of new drugs. We utilize a variety of animal models including genetically modified mice, zebrafish, and other species to accurately simulate human disease conditions. Our research focuses on evaluating drug efficacy in vivo, measuring key endpoints such as tumor growth inhibition, survival rates, and organ-specific responses. This approach ensures data validity within a systemic, whole-body context. We construct various animal models and their applications as follows:

In Situ Models for Drug Screening

In situ models initiate tumors within animals via carcinogen application or genetic engineering, providing access to all stages from initiation to metastasis. They allow observation of tumor and microenvironment co-evolution within a complete immune system background. We develop complex, genetically engineered animal models like the KPC model, which conditionally expresses mutated forms of KRas and p53 for evaluating immunotherapy efficacy.

GEM-Derived Transplant Models (GDAs) for Drug Screening

GEM-derived transplants (GDAs) involve implanting GEM tumor fragments into immunocompetent recipient animals. This approach bypasses the slow progression and asynchronous issues of in situ models. We help create GDA libraries, utilizing their diversity for therapeutic testing and biomarker discovery in drug screening.

Cell Line-Derived Transplant Models (CellDAs and CellDXs) for Drug Screening

Cell line-derived syngeneic transplants (CellDAs) and xenografts (CellDXs) balance realism and operability in animal models. They are suitable for studying therapeutic interventions and allow for genetic manipulation in vitro, facilitating gene screening during drug screening studies.

Patient-Derived Xenograft Models (PDXs) for Drug Screening

Patient-derived xenograft models (PDXs) maintain the original genome and phenotypic diversity of human tumors. They are ideal for replicating human tumor heterogeneity and overcoming the limitations of GEM models and established tumor cell lines in drug screening applications.

Our animal services uphold rigorous ethical standards and compliance with international regulations, ensuring the ethical treatment and welfare of all experimental animals. We prioritize animal welfare through professional team training, continuous monitoring, and adherence to the 3R principles—Reduce, Refine, and Replace. Collaborating closely with regulatory bodies and partners, we ensure our practices meet industry standards, promoting responsible scientific research while safeguarding animal rights.

Background

Despite significant advancements in science, metastatic diseases remain challenging to treat. Hence, researchers urgently need better insights into mechanisms of metastasis, tumor evolution, and drug resistance. Accurately replicating complex tumor ecosystems through sophisticated preclinical models is crucial to achieving these goals.

Advantages of Animal Models

The focus of cancer therapy has shifted towards strategies including immunotherapy and anti-angiogenesis, which indirectly target tumor cells by reprogramming the tumor microenvironment. Animal models offer a more comprehensive and human-like approach to reconstructing tumor ecosystems than most simplified models. Their advantages include:

1. Coverage of Tumor Progression Stages: Capable of spanning all stages from initiation to metastasis for natural history and intervention studies.

2. Similar Complexity to Human Tumor Microenvironment: Reflecting the complexity of human environments, enabling assessment of genetic or drug interventions within the tumor ecosystem.

3. Evaluation of Genetic or Drug Intervention Effects: Assessing effects within the tumor ecosystem background.

4. Utilization of Advanced Imaging Techniques: Facilitating dynamic observation of tumor progression.

Technological advancements in animal modeling have progressed from models reliant on carcinogens and transplanted tumor cell lines to highly complex genetically engineered models (GEMs). The evolution of genome engineering, particularly CRISPR/Cas technology, allows precise gene editing or selective gene activation/deactivation at any point within the tumor ecosystem, revealing their contributions to tumor initiation processes.

Figure 1. Phenotypic screening and validation using animal model. (Zhu Y, et al., 2022)

Challenge & Solution

Addressing Challenges in Disease Animal Model Development: Creative Biogene's Comprehensive Solutions

The main challenges currently faced by the pharmaceutical industry in the development of disease animal models include: limited model diversity and difficulty in simulating disease symptoms and characteristics, neglect of clinical needs, significant phenotypic differences between humans and mice, limited gene editing technology, and insufficient in vivo tracking methods. As an industry leader, Creative Biogene provides comprehensive solutions to address these challenges.

• Diversified Model Development: We specialize in developing diverse animal models, including those for rare and genetic diseases, along with customized model design services. This enables more precise simulation of different disease pathologies and clinical characteristics.
• Clinically Oriented Research Design: Placing clinical needs at the forefront, we tailor personalized research plans and model designs based on a deep understanding of our client's specific research objectives and clinical backgrounds. This ensures the development of animal models that better meet real-world clinical application needs.
• Advanced Gene Editing Technologies: We employ cutting-edge gene editing technologies such as CRISPR/Cas9 to precisely control gene activation and deactivation. This enhances our ability to accurately mimic genetic features and phenotype changes of human diseases, thereby improving model predictability and reliability.
• Innovative Imaging and Analysis Technologies: By integrating advanced imaging techniques and multidimensional data analysis, we provide efficient and precise methods for evaluating and validating drug efficacy within animal models. This helps clients gain comprehensive insights into drug mechanisms and effects, accelerating the process of new drug development.

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Exploring Infinite Possibilities in Life Sciences

Animal models excel in validating drug targets, assessing potential toxicities, establishing drug mechanisms, and identifying treatment tolerances. They are crucial platforms for developing predictive biomarkers, particularly in the application of immunotherapy drug development.

Creative Biogene is committed to providing advanced and precise animal model efficacy assessment services, facilitating the transition of new drugs from the laboratory to clinical settings. By leveraging these complex models, we better understand disease mechanisms, improve drug development success rates, and drive scientific advancements.