The SRG Rat®

Sprague Dawley-Rag2em2heraIl2rgem1hera/HblCrl

A Highly Immunodeficient Rat Strain for Xenograft Studies

The SRG rat is a SCID model created through knockout mutations in the Rag2 and Il2rgamma genes that result in a loss of mature B, T, and NK cells. the SRG Rat has an immunodeficient phenotype ideal for the engraftment of human tissue.

Taking advantage of the Sprague Dawley background and the larger organism size, SRG users have found our rats uniquely optimal for combining efficacy, pharmacokinetic (PK), biomarker, and toxicology related endpoints.

Get the most out of the SRG Rat model by leveraging our preclinical oncology expertise. In the hands of our seasoned researchers, the rat can deliver robust data, faster.

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What’s Unique About The SRG Rat Model?

While some immunodeficient rodent strains such as the Nude rat are partially immunodeficient missing T-cells, this enhanced immunodeficient rat model has a severely impaired immune system lacking B-cells, T-cells, and NK-cells.

The SRG Rat model demonstrated enhanced utility such as high tumor takes and favorable growth kinetics for both cancer cell-line xenografts and PDX models. The model overcomes the limitations of smaller mouse models enabling larger tumor growth, easier surgeries, and more tissues and serum for analyses, including repeat sampling.

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Xenograft & PDX Studies 

Hera provides in vivo oncology studies in our SRG rat in wide variety of xenograft and PDX tumor models.  Learn more about why researchers prefer our SRG rat over traditional mouse models.

Or request more information about our capabilities and expansive xenograft portfolio.  Let our team of expert scientists advise on the selecting the perfect preclinical drug efficacy testing strategy.

Preclinical Oncology Services

Exclusive SRG distribution partnership
with Charles River

Charles river logo

Hera has partnered with Charles River for the distribution of the SRG rat to the directly to the global research community.  Now all rat orders will be placed with and fulfilled by Charles River.

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Validated Using Difficult Xenograft and Patient Derived Xenograft (PDX) Models

The SRG Rat has been validated using a wide range of xenografts that consistently demonstrate high tumor take rates with traditionally difficult to engraft cell lines, such as VCaP prostate cancer, H358 non-small cell lung cancer (NSCLC), and prostate, NSCLC, and ovarian PDX models.

Additionally, humane endpoints allow for subcutaneously implanted xenograft and PDX models to reach 10X tumor volumes, up to >20,000 mm3, compared to mouse xenografts allowing for serial tumor sampling or faster PDX establishment.

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How Is The SRG Rat Better Than SCID Mice?

Through the use of the SRG Rat, researchers can collect more consistent, higher quality data that provides advantages for predicting success in the clinic.

Xenografts in the larger SRG Rat models can display vastly improved engraftment efficiencies, tumor size, growth, and tumor morphology across a number of human cancer cell lines and patient-derived tissues that are either not permissive or extremely inefficient in mice.

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srg oncorat provides better tumor take rates, larger tumor volumes, and a more human-like metabolism

Cancer Researchers Find Success With SRG Rat Models

A team of researchers led by Dr. Ramesh Narayanan at the University of Tennessee partnered with Hera BioLabs to evaluate new therapeutics for castration-resistant prostate cancer (CRPC), targeting androgen receptors (ARs).

Given the need for prostate cancer xenografts which model high AR-expression amplification phenotype found in many CRPC patients, the SRG rat has high tumor take rates of prostate cancer xenograft cell lines such as LNCaP & VCaP (>90%) which are prohibitively inefficient in mouse. Hera has expanded our capabilities to include validated castration-resistant and enzalutamide-resistant models.

“The tumor uptake rate was to 80-100%, which is a huge advantage because what we could achieve as a statistical significance with 8-12 mice, can be achieved with 5-6 OncoRats.”

Ramesh Narayanan, Ph.D.

Associate Professor of Medicine & Hematology
University of Tennessee Health Science Center

Learn more by downloading our case study.

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Accelerate Your Pre-Clinical Cancer Research and Drug Development

Contact us to learn more about how you can leverage the SRG rat to boost your research.

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Creating the SRG Rat

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 Rat 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 in 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. The SRG Rat (or 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 and in pharmacology and toxicology with a humanized hepatocyte SRG Model – HepatoRat™. 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.

Additional Resources

We have compiled answers to frequent questions about our novel SRG OncoRat®. If you still have questions, feel free to contact us.

What is the SRG Rat?

The Sprague Dawley-Rag2-Il2rg knockout rat strain is commonly referred to as the SRG Rat or the OncoRat. It has a Sprague Dawley background containing a double knockout of the Rag2 and 112rg genes. The combined mutations result in a loss of mature B, T, and NK cells and the most severely immunodeficient rat model on the market.

The SRG Rat was created by Transposagen Biopharmaceuticals, Inc. and transferred to Hera BioLabs, Inc. in 2015. Hera exclusively partnered with Charles River Labs for distribution to the research community.

What services does Hera provide?

Hera provides in vivo contract research (CRO) services in the SRG rat and immunodeficient mouse strains including xenograft/PDX studies, pharmacology, toxicology studies with a variety of treatment routes and endpoints on preclinical small molecules, antibodies, cell and gene therapies, and medical devices. Find out how we can use a combination of endpoints to get the most relevant data out of your animal studies. All in vivo studies are conducted in our state-of-the-art facility located in Lexington, KY.

What cancer types grow in the SRG rat?

The SRG rat is an ideal host for cancer xenografts (or PDXs) because it is highly immunodeficient. Almost all cancer types have been tested in the SRG rat which generally demonstrates highly uniform tumor growth and nearly 100% tumor take-rates. Contact us for a full list of models validated in the SRG including those with in vivo standard of care data.

Can the SRG rat be humanized?

The SRG is amenable to engraftment of human tissue(s) including those used for humanization of the immune system and humanization of the liver. Hera is developing several ways to humanize the immune system including PBMC engraftment, hematopoietic stem cells, and the BLT method with the goal of creating a platform for studying immunotherapies, GVHD, and infectious diseases. Hera is developing a humanized rat model for pharmacology, toxicology, and other applications (learn more).

What are the applications of the SRG rat?

The SRG rat can be used in the place of any immunodeficient mouse strain, while providing many advantages such as larger sample collection, a more translational metabolism, easier surgeries, etc. In addition to oncology and immuno-oncology applications, the SRG rat can also be used for medical device implantations, allografts/regenerative medicine, hearing or ocular assessments, as well as provide pharmacology and toxicology endpoints on the preferred Sprague Dawley background alongside efficacy data.

Can the SRG rat be used for continuous IV dosing?

Hera can provide SRG rats that have undergone implantation of Vascular Access Buttons (VABs) and other surgeries conducted by Charles River surgeons at their facility prior for studies conducted by Hera or direct shipment to your facility. The larger size of the SRG rat makes it an ideal host for implanted pumps (Alzet or Iprecio). Contact us for more details and pricing.

How many cancer cells should I use for my xenograft/PDX?

The SRG rat is highly amenable to engrafting human xenografts and PDXs. For studies we conduct on behalf of our clients, we typically implant between 1 and 10 million cancer cells into the subcutaneous space. When implanting a PDX, Hera uses a 2 x 2 x 2 mm tissue piece subcutaneously into each SRG rat. Each xenograft model will exhibit different tumor growth kinetics and we recommend a quick in vivo pilot study to assess your model prior to running a drug efficacy study.

Can I purchase SRG Rats for my research?

Hera has licensed the SRG rat to Charles River for distribution directly to the global preclinical research community. As of April 15, 2022, all orders will be placed with and fulfilled by Charles River. Orders can be placed on the Charles River website HERE.

Do the SRG rats require a special diet or housing conditions?

SRG rats should be housed in IVC cages or a barrier facility, if possible. Their immunodeficient phenotype leads to a susceptibility to opportunistic pathogens which should be taken into consideration, as is the case with any immunodeficient strain. Other than that, the SRG does not require any special diet or care and maintenance procedures. Standard irradiated rodent chow is used.

 For a full list of resources on our SRG rat please visit our PUBLICATIONS page.

  1. Noto, F. K., Adjan-Steffey, V., Tong, M., Ravichandran, K., Zhang, W., Arey, A., McClain, C. B., Ostertag, E., Mazhar, S., Sangodkar, J., DiFeo, A., Crawford, J., Narla, G., & Jamling, T. Y. (2018). Sprague Dawley Rag2-Null Rats Created from Engineered Spermatogonial Stem Cells Are Immunodeficient and Permissive to Human Xenografts. Molecular cancer therapeutics, 17(11), 2481–2489. https://doi.org/10.1158/1535-7163.MCT-18-0156
  2. Ponnusamy, S., He, Y., Hwang, D. J., Thiyagarajan, T., Houtman, R., Bocharova, V., Sumpter, B. G., Fernandez, E., Johnson, D., Du, Z., Pfeffer, L. M., Getzenberg, R. H., McEwan, I. J., Miller, D. D., & Narayanan, R. (2019). Orally Bioavailable Androgen Receptor Degrader, Potential Next-Generation Therapeutic for Enzalutamide-Resistant Prostate Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, 25(22), 6764–6780. https://doi.org/10.1158/1078-0432.CCR-19-1458 
  3. Maulhardt, H. A., Hylle, L., Frost, M. V., Tornio, A., Dafoe, S., Drummond, L., Quinn, D. I., Kamat, A. M., & diZerega, G. S. (2019). Local Injection of Submicron Particle Docetaxel is Associated with Tumor Eradication, Reduced Systemic Toxicity and an Immunologic Response in Uro-Oncologic Xenografts. Cancers, 11(4), 577. https://doi.org/10.3390/cancers11040577

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