Biocytogen provides one-stop solutions for next-generation drug development, from target to IND application to the global biomedical communities. Empowered by its cutting-edge gene editing technologies and state-of-art animal facility, Biocytogen developed a seamlessly integrated platform for efficient antibody drug discovery. The technical teams in Bicytogen support a comprehensive portfolio of products and services, covering in vivo/in vitro preclinical services, animal model generation, fully human antibody (via RenMab™ Mouse), therapeutic antibody discovery and development services, CMC/CDMO, and regulatory affairs support. Biocytogen collaborates with more than 70% of top 50 pharmaceutical and numerous biotech start-up companies worldwide. Together, we discover innovative medicines for a better, healthier world.
RenMab Mouse Antibodies
Biocytogen’s RenMab™ Mouse is an antibody-humanized mouse with the most complete antibody genes replacement in the world, which has been designed to greatly simplify and de-risk the antibody development process. In the RenMab™ Mouse,
1. The parts of the genes that encode for antibody variable domains of H and κ chains are replaced in situ by human sequences using a unique chromosome engineering technique, while the constant domains and critical regulatory elements remain murine.
2. The RenMab™ Mouse has a normal immune system comparable to that of the wild-type mouse. Because of the higher diversity of its antibody genes, the RenMab™ Mouse has a higher potential for antibody drug development.
3. The RenMab™ Mouse is the ideal platform for researchers to generate fully human antibody-based drugs with strong specificity, high affinity, and diversity.
Biocytgoen offers an array of double and triple humanized mice for combination therapy in vivo efficacy studies.
See the link below for further information: https://biocytogen.com/products/humanized-immune-checkpoint-mice/
The Immune-deficient B-NDG mouse model (NOD-Prkdcscid IL2rgtm1/Bcgen) was independently designed and generated by Biocytogen. B-NDG mice are generated by deleting the IL2rg gene from NOD-scid mice with severe immunodeficiency phenotype. Lacking mature T cells, B cells or functional NK cells, and displaying cytokine signaling deficiencies, this mouse model has the highest degree of immunodeficiency and thus is most suitable for engraft and growth of human hematopoietic stem cells (HSCs), peripheral blood mononuclear cells (PBMCs) and human tumor cells or tissues.
Advantages of B-NDG Mice
Biocytogen offers industy leading models of humanized immue-checkpoints and cytokines/cytokine receptors. Please see our website for more information:
Definition: A mouse model with a functional human gene, cell, tissue, or organ, which is used as living body substitution model for human disease study. This service refers to the model with the functional human gene.
Advantages: the human gene is expressed in the mouse body using the promoter and regulation region of the mouse gene.
Disadvantages: to ensure that the human gene is physiologically expressed and regulated normally in the mouse genome, the sequence and structure information of the genes and proteins should be analyzed in depth before designing, and comprehensive risk assessments should be built.
A humanized mouse model with a functional human gene is constructed by replacing part or all of the mouse gene with the human gene. The expression of the human protein in the mouse body is the same as the mouse protein’s expression, but the protein or functional region(s) of the mouse protein is not expressed in any cells or tissues.
Brief introduction of the technology
TALEN (Transcription Activator-Like Effector Nuclease) is another high-efficiency genome modification tool. Its high efficiency, strong specificity, low missing rate, and simple design makes the technology widely used for gene knockout and genome modification at the cell and in vivo levels.
BIOCYTOGEN provides services for mouse model construction in one step, including model designing, construction, and genotypic identification service
BIOCYTOGEN possesses a senior technical team specializing in comprehensive analysis of project feasibility, and provides a free and professional model design service. The services include:
Ÿ Define the purpose for constructing the model
Ÿ Analyze the target gene’s structure and sequence information
Ÿ Analyze existing data
Ÿ Design all possible model construction schemes
Ÿ Analyze the advantages and risks of all model construction schemes
Ÿ Accurate prediction of project implementation time and quotation
Design and construction of TALEN
Ÿ Pronuclear injection of the mRNA (TALEN) into the mouse zygotes
Ÿ Recipient female mouse feeding and the birth of chimeric mouse
Ÿ Mating of chimeric mouse and wild mouse
Ÿ Birth of generation F1 mice
Ÿ Ensure the phyla heredity by identification of generation F1 mouse tail genotype
Use the homologous recombination technology to replace all the exons, several important exons, or function domains of a target gene using a section of exogenous DNA sequence, and obtain a mouse model where all of the tissues and cells during all developmental stages (from 1-cell embryo to adult stage) do not express the gene.
Advantages and disadvantages:
The conventional knockout realizes the target gene knockout by replacing one or more exons of the target gene using the screening gene neomycin (Neo). The knockout occurs in all of the tissues and cells in the body, which includes the risk of embryonic death. This risk can be avoided by a conditional knockout strategy.
*Pharmacological and pharmacodynamic test for CDX (Cell line-Derived Xenograft) tumor model* CDX (Cell line-Derived Xenograft) is a well established model for the research and development of tumor drugs. The model is easy to establish and has excellent repeatability, so it is still under high demand for the research and development of tumor drugs.
Cell line models are established by inoculating passage tumor cells in vitro, and culturing them into the body of immune deficient mice
Targeting Vector Construction Services
Definition: mouse models with single or multiple base changes or an exogenous gene introduced into the target gene position.
Principle: Knockins introduce specific mutation(s) or an exogenous gene in the target gene position. For example, this method can introduce point mutation(s), which can simulate a human genetic disease, in the target gene. It can also be used to introduce a reporter gene (such as EGFP, mRFP, mCherry, mYFP or LacZ, etc.) or functional cDNA (such as Cre and Dre, etc.) to be expressed in a specific locus by homologous recombination, thereby making the expression of the reporter gene or other cDNA accordant with the expression of the target gene. The knockout and knockin occurs at the same time when the reporter gene or cDNA replaces the mouse gene.
Using the EGE system, EGFPand mCherrygenes are knocked into the ACTB and LMNB1 translation initiation sites, respectively, in the rodent C6 cell lines.
By using flow cytometry analysis, we have found that the CRISPR/Cas9 mediated gene EGFP-ACTB knockin in efficiency is only 1.91% in U2OS cells while the efficiency is 15.02% by using EGE system, which shows an 8-fold increase. In C6 cell line, the EGFP-LMNB1 knockin efficiency increased from 0.19% to 3.6% by using EGE system, which is about a 19-fold increase.
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