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Genome-edited Animal Model Development Service
Introduction
Utilizing techniques like embryo microinjection, ESCs (Embryonic Stem Cells), viral delivery, and somatic cell editing, BioVenic's genome-edited animal model development service can be carried out in laboratory animals, including mice and rats, as well as companion animals such as dogs, and includes subsequent animal experiments, biological sample collection, and analysis projects.
BioVenic Genome-edited Animal Model Development Services
Development of Genome-edited Animal Models
BioVenic offers clients the service of generating various types of genome-edited animal models based on the models that you desire to develop. Common genome-edited animal models include the following services:
Table. 1 Common Genome-edited Animal Model Development Services
| Service Type | Purpose | Main Applicable Species |
|---|---|---|
| 1. Gene Knock-Out (KO) / Knock-Down (KD) Models | To completely abolish or significantly reduce the function of a specific gene. | Mice/Rats, Zebrafish, Rabbits |
| 2. Gene Knock-In (KI) / Humanized Models | To precisely replace or insert a new DNA sequence at an endogenous locus, often replacing an animal gene with a human homolog, or inserting a reporter gene. | Mice, Rats, Pigs |
| 3. Conditional Knock-Out (cKO) Models | To achieve gene deletion specifically in certain tissues or at a particular time point using the Cre-LoxP or FLP-FRT system. | Mice, Rats |
Validation of Genome-edited Animal Model Generation
1. Genotype Identification (Molecular Level): PCR amplification and restriction enzyme digestion, Sanger sequencing, Next-Generation Sequencing (NGS), off-target prediction and validation.
2. Transcriptional Level Validation: RT-qPCR, RNA-seq.
3. Protein Level Validation: Western blot / ELISA, Immunohistochemistry (IHC) / Immunofluorescence.
4. Phenotype Validation (Functional Level): Physiological/ metabolic indicators, behavioral experiments, histological/ morphological observation, functional experiments.
Genome-edited Animal Model Sample Collection Service
After confirming the experimental objective, the required sample type (blood, tissue, urine, feces, saliva, etc.), the sample volume, and the client's requirements, BioVenic can assist clients with the collection of biological samples from the animal models. Subsequent analysis of biological targets in the relevant samples can then be performed.
Research Services Conducted on Genome-edited Animal Models
Once the animal models are constructed, BioVenic can provide various services according to the client's needs, including:
- Animal Histopathology Service
- Animal Cytology Service
- Animal Behavioral Analysis
- Animal Imaging Service
- Preclinical Animal Pharmacokinetics (PK) Study
- Preclinical Animal Pharmacodynamics (PD) Study
Learn about other BioVenic animal model induction methods:
- Chemically-induced Animal Model Development
- Diet-induced Animal Model Development
- Surgically-induced Animal Model Development
- Biologically-induced Animal Model Development
Typical Development Workflow for a Genome-edited Animal Model
Fig. 1 Steps for constructing genome-edited animal models. (BioVenic Original)
Genome-editing Methods for Animal Model Development
BioVenic utilizes important gene editing methods for developing animal models. These methods are essential tools that drive basic biological research by creating animal models to study gene function, and they are vital for translational medicine, allowing the development of accurate disease models and the testing of new therapeutics and diagnostics.
Table. 2 Common Genome-editing Methods for Animal Model Development
| Methods | Ease of Design | Efficiency/Speed | Cost | Main Applications |
|---|---|---|---|---|
| Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9 System | High (simple gRNA design) | Very High (Fast) | Low | KO, KI, cKO, single-gene/multiplex editing |
| Transcription Activator-Like Effector Nucleases | Medium (modular protein design) | Medium-High | Medium-High | Targeted KO and KI (less used now) |
| ES Cell Targeting | Medium | Low (Slow) | High | Historically, complex KIs and cKOs (mostly superseded) |
Fig. 2 In vivo delivery methods used for animal genome editing.1,3
Common Applications of Genome-Edited Animal Models
Gene editing technology plays a crucial role in the construction of animal models, and disease models in various research fields can be created using gene editing techniques. BioVenic's Genome-Edited Animal Model Development Service offers significant advantages over conventional induction and surgical model construction methods and can be utilized in many primary research fields.
Table. 3 Common Gene-Edited Animal Models and Their Applications
| Species | Common Gene-Edited Model Examples | Primary Research Fields |
|---|---|---|
| Mice |
Humanized Models: Human immune checkpoint targets (e.g., PD-1/CTLA-4), human cytokine receptors. Disease Models: Cancer (GEMM), Alzheimer's, Duchenne Muscular Dystrophy (KI/KO models). |
|
| Rats | Disease Models: Cardiovascular (Hypertension, Atherosclerosis), Diabetes, Neurobehavioral disorders (Depression, Anxiety). |
|
| Zebrafish |
Disease Models: Leukemia, Melanoma, Congenital Heart Disease. Tool Models: Fluorescent reporter lines (for developmental tracking or pollution detection). |
|
| Pigs |
Humanized Models: Knockout of immune rejection genes for xenotransplantation. Disease Models: Cystic fibrosis, Cardiovascular disease, Dermatology. Agricultural Traits: Disease resistance (e.g., PRRSV), lean meat. |
|
| Cattle & Sheep |
Agricultural Traits: Increased milk yield, disease resistance (e.g., Bovine Tuberculosis resistance). Disease Models: Neurological disorders (e.g., Lysosomal Storage Disorders in sheep). Bioreactors: Production of therapeutic proteins in milk. |
|
| Chickens |
Agricultural Traits: Enhanced laying performance, viral resistance (e.g., Avian Flu, Leukosis). Bioreactors: Production of recombinant proteins in egg white. |
|
| Dogs & Cats | Disease Models: Inherited genetic diseases (e.g., DMD), retinal diseases. |
|
Case Study: Humanized PCSK9 Knock-in (KI) mice
BioVenic offers full-service support for the creation and testing of humanized mouse models by using high-precision genomic integration. Humanized PCSK9 Knock-in (KI) mice facilitate research on hypercholesterolemia. Scientists have successfully replaced murine loci with human-specific sequences, making an environment that is "trial-ready" and accurately mimics human disease phenotypes, like high LDL cholesterol levels. To guarantee the highest level of reliability for preclinical pipelines, they enhance model production with a comprehensive validation suite. This suite includes NGS-based genomic integrity audits, human-specific protein quantification, and functional efficacy testing using advanced tools like base editing. NGS-based deep sequencing helps to confirm precise insertion and verify the absence of off-target effects. Human-specific ELISA and Western Blotting to quantify circulating human PCSK9 levels. Longitudinal monitoring of serum lipid profiles to ensure a robust and reproducible disease phenotype. This allows them to assess the pharmacodynamics of human-targeted therapeutics with unparalleled precision. By combining advanced genome editing technologies with stringent functional validation, we develop high-performance animal models that bridge the gap between genetic design and clinical efficacy. Our humanized cardiovascular models offer a reliable path for the preclinical evaluation of next-generation genetic medicines.
Fig. 3 Generation and characterization of a human PCSK9 knock-in mouse model.2,3
Advantages of BioVenic Genome-edited Animal Model Development Service
In-depth Feasibility Assessment and Analysis before Project Commencement
BioVenic provides a more rational model design to prevent artifactual phenotypes caused by inappropriate construction strategies. Our scientists offer a more detailed project feasibility assessment. Following this evaluation, BioVenic team can provide an estimated project workflow and timeline.
Comprehensive Research Platform
BioVenic do not just offer model generation services; we can also address clients' research needs by providing cell and tissue sampling services, detection services for large molecules/metabolites related to research targets, and a variety of scientific research services (including non-GLP pharmacodynamic evaluation services, diverse animal experimental studies, and histopathology studies).
Broad Research Scope
BioVenic's technical platform is capable of comprehensively applying genome-editing strategies to provide various model generation services across different research areas (Oncology, Nervous System, Immune System, Metabolism and Nutrition, Cardiovascular System, and other diseases).
FAQs
Do you provide live model animals?
We currently do not provide live animals. We offer gene-edited animal model development services, as well as subsequent services such as cell and tissue sampling, detection services for large molecules/metabolites related to research targets, and various scientific research services (including non-GLP pharmacodynamic evaluation services, diverse animal experimental studies, and histopathology studies).
What are the advantages of gene editing methods over other methods in animal model development, and can you provide an example?
Gene editing technology is better than traditional ES cell or random transgenesis methods because it is faster, cheaper, more effective, and more accurate. These methods have problems like long timelines, species restrictions, and low success rates. It allows for the creation of animal models that more accurately replicate human disease phenotypes in either a single-step or multi-gene simultaneous approach. The DMD (Duchenne Muscular Dystrophy) mouse model exemplifies its practical application, showcasing the significant potential of gene editing in disease mechanism investigation and therapeutic evaluation.
Can you provide a project timeline and quotation?
Based on the type of animal model you need, the species of animal, and the information of the gene to be edited, BioVenic team will need to conduct an assessment considering your budget and the required species & strain, target gene, editing type, validation depth, and subsequent service needs. As a reference, the project cycle for constructing a mouse model (common strain) is approximately 9 to 12 months.
Contact Us
BioVenic's gene-edited animal model development service can help researchers conduct various genetic modifications in laboratory animals, as well as in companion animals and livestock, based on their research needs. BioVenic also provides validation of the gene-edited animal model generation, animal model sampling services, and subsequent research services conducted on the animal models. If you are interested in our gene-edited animal model development service, please feel free to contact us and inform us of your research needs and the species of animal model you wish to construct. BioVenic's researchers will assist with a feasibility assessment, dedicated to providing a suitable model for your subsequent research.
References
- Lee, Hyunji, Da Eun Yoon, and Kyoungmi Kim. "Genome editing methods in animal models." Animal cells and systems 24.1 (2020): 8-16. https://doi.org/10.1080/19768354.2020.1726462. The original title was changed to "In vivo delivery methods used for animal genome editing".
- Carreras, Alba et al. "In vivo genome and base editing of a human PCSK9 knock-in hypercholesterolemic mouse model." BMC biology vol. 17,1 4. 15 Jan. 2019, https://doi.org/10.1186/s12915-018-0624-2 . The original title was changed to "Generation and characterization of a human PCSK9 knock-in mouse model".
- Distributed under Open Access license CC BY 4.0.