Tackling Polygenic Diseases – Chimeron Bio’s Combination RNA Drug Platform is Pushing the Field

February 12, 2020  |  By Chimeron Bio  |  2 Minute Read

RNA is a highly versatile and potent molecular regulator of biological processes. While an understanding of the different types of RNA has spearheaded the field of RNA therapeutics, we are yet to see the fullest exploitation of this molecule in drug discovery.  Part of the reason is that the RNA therapy space is highly segmented with drugs being developed to either address a missing gene (mRNA technologies) or silence a mutated or bad gene (siRNA and miRNA technologies).  However, if we combine both these technologies, we could fully deploy the power of RNA drugs and tackle more complex diseases including polygenic disorders (caused by the action of 2 or more genes). For example, to treat certain cancers and rare genetic disorders, there is a need to not only introduce multiple missing genes, but also knock-down or lower the mutated genes at the same time.  In such situations, drugs designed to either express only a single gene (lipid coated mRNA or AAV containing DNA) or silence the mutant gene with siRNA oligos address only a part of the manifestations and confers only part of the benefits (see figure).  A technology with broader applicability and RNA delivery capabilities, is therefore an attractive option.

The key technological considerations to develop RNA therapies for polygenic disorders include, 1) Cargo size: can a single particle accommodate multiple genes? 2) Cargo versatility- can a single delivery particle accommodate multiple RNA species? and 3) Long term safety implications: will the cargo integrate into the host genome?

At Chimeron Bio, we are developing drugs that that are designed to tackle diseases broadly, either by simultaneously introducing a cascade of genes or by delivering oligos designed to both overexpress the missing genes and silence the mutant genes (see figure).  Our proprietary ChaESAR^TM particles are designed to and can package multiple genes and multiple RNA types (mRNA, small oligos) within the same particle and maintain tissue tropism.  Furthermore, our technology is non-replicating and non-integrating and well tolerated in early preclinical studies.  Finally, the self-amplification aspect of the ChaESAR^TM particle allows lower dosing compared to other leading gene and DNA-based therapy technologies.  RNA therapeutics offers a cleaner (non-integrating) and a more direct way to restore normal biology in cells, and Chimeron Bio is committed to advancing this field to help patients. 

We at Chimeron Bio believe that ChaESAR^TM technology can have a broad impact across therapeutic areas and are actively investigating ChaESAR^TM drugs in cancer and rare gene disorders of the liver and kidney.  Find out more about our technology, vision and team at www.chimeron.com