SCID RAT MODEL

The SRG Platform, is a Sprague-Dawley rat with a double knockout for the Rag2 and Il2rgamma genes (SD-Rag2tm2hera Il2rgtm1hera ). SRG is a severely immunodeficient rat that lacks B-cells, T-cells, and NK-cells. The OncoRat® was the first model built on the SRG Platform and introduced to enable and accelerate xenograft efficacy studies.

Background

Cutting-edge gene-editing technologies Cas-CLOVER™ and piggyBac™ enable Hera to precisely engineer animal models and cell systems. Due to limitations of mouse models for oncology and the improved translatability of rats; Hera set out to create the ultimate rat model for oncology. The SRG Platform was created through targeted-nuclease mediated gene disruption of the rat Rag2 and II2rg genes. It contains an 8 bp deletion in the Rag2 gene causing defective V(D)J recombination preventing T cell and B cell development. SRG also has a 16 bp deletion in the Il2rg gene, which leads to a lack of cytokine signaling, resulting defective lymphoid development. The combined mutations result in a SCID rat with loss of mature B, T, and NK cells.

Phenotype & Applications

The SRG has a SCID rat phenotype and accepts human tissue as a xenograft model. OncoRat has been validated with a wide range of xenograft models including patient derived xenografts (PDX) and consistently demonstrates improved tumor take-rates and delivers tumor sizes 10x that of mouse models in half the time. For translational research, the rat produces blood and tissue samples ten times larger than mice and is metabolically closer to humans. Since the rat is the preferred model for pharmacokinetics (PK) and toxicology, OncoRat is ideally suited for efficacy and PK/toxicology studies in the same animal.

The SRG Platform can also be reconstituted with human immune cells such as PBMCs to produce humanized rats, the ImmunoRat™ – is in development for immune-oncology studies. Hera and its collaborators continue to develop additional applications of the SRG Platform. Please contact us if you have questions about applications outside of oncology and immune-oncology.

Immunophenotype of the SRG Platform

Analysis of immune populations in SRG rats. A) CD4+/CD8+ mature T cells are absent. B) The spleen contains no mature B cells as demonstrated by lack of CD45R (B220)+/IgM+ cells. C) The Il2rg knockout results in a reduced NK cell population in the spleen.

Comparison between Nude rats and the SRG rat show a severally reduced number of natural killer (NK) cells in the circulating blood.

OncoRat® is a registered trademark of Transposagen

piggyBac™ is a trademark of Transposagen

Cas-CLOVER™ is a trademark of Poseida Therapeutics

SRG™ is a trademark of Hera BioLabs