Gene editing is getting a lot of attention in the oncology field for its potential in gene therapy, but this only scratches the surface of its potential applications. Hera is now using it to fight cancer through the creation of genetically engineered rat models for preclinical drug discovery. The rat has been the preferred model of toxicology and drug efficacy studies for decades because the mechanisms of drug processing, action, clearance, and toxicity are more similar to humans than mouse models. In the past decade, genomic editing of laboratory rat models has made substantial advances in their utility as tumor xenograft hosts – with tumor growth profiles and cellular fidelity far exceeding the best statistics in matched mouse models.

 

Hera Biolabs has used its proprietary gene editing technologies to develop multiple rat models that are genetically ideal for use in pre-clinical oncology research by oncology CROs. The first of these is a Sprague Dawley Rag2 null rat (SDR rat) which features a lack of mature B cells and severely reduced T-cell population. This specific strain was produced using cutting-edge transcription activator-like effector nuclease (TALEN) technology to target the Rag2 locus resulting in an in-frame deletion. Hera has developed other novel rat models that are ideal for oncology CRO research using various targeted nucleases.

 

Demonstrating our further commitment to preclinical oncology research and the support of oncology CROs, Hera has gone one step further and created the OncoRat®. The OncoRat was designed to overcome possible limitations of the SDR rat for some human tumor types due to the NK-cell population remaining intact in the SDR rat. The OncoRat is T-cell, B-cell, and NK-cell deficient and boasts improved engraftment rates, rapid growth kinetics, and enables faster PDX studies in fewer passages.

 

The production of these rat models demonstrate Hera Biolabs’ commitment to use cutting edge genome-editing tools to create novel, precise, and superior translational research models. Hera’s genomic editing arsenal boasts a dimeric CRISPR system that features Cas-CLOVER™, with limited off-target mutations, which can be integrated with the piggyBac™ transposon to permit scarless gene editing. This scarless gene editing approach allows Hera to create isogenic cell lines to help our clients answer questions about specific mutations or mechanisms of action they are studying. The use of gene editing to create isogenic cell lines allows these studies to be performed more efficiently and effectively by eliminating the effects of other driver and passenger mutations. It has also been suggested that using these gene editing techniques to produced isogenic cell line models from multiple tissue types will help elucidate the similarity between mechanisms across tissue types1. This could have wide implications for the broad spectrum of personalized medicine initiatives oncology CROs aim to invest their efforts in.

 

Hera is dedicated to providing high-quality oncology CRO services powered by their gene editing technology and current R&D efforts which include developing a humanized immune system and liver in the OncoRat.

 

1. Wilding, J. L.; Bodmer, W. F., Cancer Cell Lines for Drug Discovery and Development. Cancer Research 2014, 74 (9), 2377-2384.