One letter. One edit. A world of difference.
Our approach
Mammals and other lower species like cephalopods have an endogenous process of modifying single bases on RNA, referred to as RNA editing. RNA editing is a natural physiological process that occurs in cells, including a mechanism mediated by an enzyme called adenosine deaminase acting on RNA, or ADAR. Our RNA editing approach involves co-opting this endogenous editing system via a proprietary engineered oligonucleotide (chemically modified RNA) to introduce precise edits.
Our platform
Oligonucleotide promoted editing of RNA (OPERA®)
We have assembled a suite of technologies and capabilities to build our RNA editing platform. OPERA relies on the following key components that enable us to generate the proprietary RNA editing oligonucleotides that form the basis of our differentiated product candidates:
Deep understanding of ADAR biology
Supported by extensive preclinical research using in vitro assays and proprietary mouse models as well as the fundamental work of our scientific advisors and founders to elucidate key insights and know-how of ADAR biology. This enables an understanding of ADAR activity in different species and disease states, allowing us to develop novel product candidates.
Expertise in oligonucleotide chemistry
Enabled by the ability to identify and incorporate chemical modifications to generate a fully modified synthetic oligonucleotide. This increases our ability to generate oligonucleotides with drug-like properties, thereby increasing the editing and translational efficiency of our product candidates.
Machine learning optimization of oligonucleotides
Driven by data science and computational capabilities for rapid design and iteration, resulting in optimal product candidates for each disease being pursued.
Fit-for-purpose delivery
Made possible by tissue-specific delivery technologies that can enhance biodistribution, specificity, durability, and editing efficiency of product candidates for each given disease.
Generation 1 designs – CHORDs™
Our first generated designs are called CHORDs (Customized High-fidelity Oligonucleotides for RNA Deamination).
Key Advantages of CHORD™
High specificity
Synthetic CHORDs enable highly precise RNA edits with a low risk of off-target edits, avoiding a key safety concern associated with DNA editing and the associated risk of aberrant genome editing.
Precedented delivery
CHORDs are delivered using clinically validated approaches, including LNPs and tissue-specific ligands (e.g., GalNAc for the liver), that enable infrequent dosing and an acceptable tolerability profile.
Transient tolerability
CHORDs are transient and reversible and carry a low risk of immunogenicity. These qualities can offer an improved tolerability profile and enable the ability to re-dose patients, which are significant advantages compared with current DNA editing technologies.
Simple manufacturing
Reliance on endogenous ADAR enzymes and the simple drug constructs of CHORDS has significant advantages, compared with the complexities of multi-component exogenous complexes used for DNA editing.
Multiple regulatory
CHORDs contain precedented chemical modifications and structural features present in several marketed oligonucleotide drugs. While guidance from the FDA and other regulatory bodies is well established for this class of therapeutics, regulators have yet to establish specific guidelines for RNA editing therapies, and clinical data has yet to be generated.
Our pipeline
Our pipeline programs demonstrate the versatility of our approach in bringing precision and tunability to genetic medicines to address a broad range of rare and highly prevalent diseases. We can repair proteins caused by genetic mutations or alter proteins to activate a biological pathway.
View our pipeline