RenMab

RenMab™: A Next-Gen Fully Human Antibody Mouse

Learn More

1. In situ gene replacement is employed in the generation of the RenMab™ Mouse

The RenMab™ Mouse was designed and developed based on Biocytogen’s unique chromosome engineering technique. In this model, the parts of the genes that encode for antibody variable domains of heavy and κ light chains are fully replaced by human sequences.

The genes (about 2.6 Mb in length) that encode for murine antibody variable domains were replaced with the human variable domains (about 1 Mb in length, containing all human V/D/J antibody genes, Figure 1A).

Genes that encode for the variable domains of human κ light chain have two copies in opposite directions, namely proximal V cluster and distant V cluster. The coding region of the proximal V cluster is intact, which is frequently selected for antibody gene replacement in other humanized mouse models. Although the distant V cluster lacks the C gene and is considered to be a pseudogene, V and J genes are still potentially functional. We replaced the genes (about 3.2 Mb in length) that encode for murine antibody variable domains with the human counterparts (about 1.6 Mb in length) containing the two opposite-direction gene copies (Figure 1B).

2. Complete human antibody germline utilization

As a result of the full humanization of the antibody gene in the variable domains, the RenMab™ Mouse expresses more diverse antibody molecules than other commercially available humanized mouse models.

The components of different antibody isotypes in the sera of the RenMab™ Mouse are nearly identical to those of the wild-type mouse. The genes that encode for human antibody variable domains in the RenMab™ Mouse can be widely used, with a full diversity of VDJ recombination as confirmed by CDR analysis. Taken together, the RenMab™ Mouse can produce a diverse repertoire of fully human antibodies for therapeutics discovery.

3. Robust Immune Response

Another major benefit of the RenMab™ Mouse’s design strategy is the maintenance of an intact immune system as confirmed by the complete analysis of the immune organs and tissues of the RenMab™ Mouse. Our data has revealed that is no significant difference between the immune cells and immune tissues of the RenMab™ Mouse and that of wild-type mouse. Such integrity of the immune system of ensure the superior efficiency of RenMab™ Mouse for the generation of antibodies over any other humanized mice models.

 

Result

Robust immune responses against strong/weak antigens were observed; Accelerated immunization strategies works also in RenMab™ mice; Optimized immunization strategies for challenging targets are available.

Result

Robust immune responses against strong/weak antigens were observed; Accelerated immunization strategies works also in RenMab™ mice; Optimized immunization strategies for challenging targets are available.

Learn how RenMab can impact your antibody discovery process

Download brochure

RenMab™ KO library

The RenMab™ KO library contains a list of RenMab™ mice each with a specific target gene knocked out. These mice are designed to elicit robust immune response against homologous proteins and generate antibodies that bind to broader epitopes.

Our Pipeline

    Validation Data

High Affinity

RenMab antibodies exhibit favorable affinity, which is one of the most important indicators of pharmacodynamic properties for antibody lead screening. We have demonstrated that RenMab antibodies can bind to antigens at sub-nanomolar range, which is on-par to wild-type murine antibodies and chimeric antibodies.

Body Weight & Spleen Weight Measurement

Result

No significant differences in average body weight and spleen weight were detected between RenMab™ Mouse and wild type mouse.

Result

No significant differences in average body weight and spleen weight were detected between RenMab™ Mouse and wild type mouse.

Immune Cell Profiling

The percentages of immune cells in spleen were analyzed by flow cytometry.

Result

In RenMab™ Mouse, the percentage of B cells,T cells, NK cells, CD4+ T cells and CD8+ T cells in spleen were identical to those of wild type mice.

B Cell Development of RenMab™ Mouse

No significant differences in average body weight and spleen weight were detected between RenMab™ Mouse and wild type mouse.

IgM and IgD expression on B220+ splenocytes were analyzed by flow cytometry. Transitional type 1 (T1, B220+IgM+IgD), Transitional type 2 (T2, B220+IgM+IgD+), Mature (M, B220+IgMlowIgD) cell population.

Result

No significant difference was observed between RenMab™ mouse and wild type mouse.

No significant differences in average body weight and spleen weight were detected between RenMab™ Mouse and wild type mouse.

CD21 and CD23 expression on the surface of B220+ splenocytes were analyzed by flow cytometry. Marginal-zone (MZ, B220+CD21+CD23) and Follicular (FO, B220+CD21LOWCD23+) B cells were quantitatively analyzed.

Result

No significant difference was observed between RenMab™ mouse and wild type mouse.

Bone Marrow B Cell Development Analysis

B cell progenitor cells in bone marrow were analyzed by flow cytometry. Base on expression levels of B220 and CD43, B cell progenitor cells in bone marrow can be divided into 3 cell populations, B220lowCD43highIgMlow (Pro-B-cell), B220lowCD43intIgMlow (Pre-B-cell), and B220highCD43lowIgMhigh (Immature-B-cell).

B220lowIgMIgDCD138+ (Plasma cell), B220+IgM+IgDCD38+ (Memory B cell) in bone marrow or spleen were also analyzed by flow cytometry.

Result

No significant difference was observed between RenMab™ mouse and wild type mouse.

B cell progenitor cells in bone marrow were analyzed by flow cytometry. Base on expression levels of B220 and CD43, B cell progenitor cells in bone marrow can be divided into 3 cell populations, B220lowCD43highIgMlow (Pro-B-cell), B220lowCD43intIgMlow (Pre-B-cell), and B220highCD43lowIgMhigh (Immature-B-cell).

B220lowIgMIgDCD138+ (Plasma cell), B220+IgM+IgDCD38+ (Memory B cell) in bone marrow or spleen were also analyzed by flow cytometry.

Result

No significant difference was observed between RenMab™ mouse and wild type mouse.

Serum Ig Subtype Analysis

Different Ig subtypes in the serum of RenMab™ and WT(C57BL/6) mice were quantitatively measured by ELISA.

Result

No significant differences in IgA, IgG1, IgG2b, IgG2c, IgG3 and IgM levels were observed.