About the Axiomer® technology
"Our Axiomer® technology enables your body to repair its own RNA specifically and reversibly." Antisense oligonucleotides (AONs) have been explored and developed as therapeutics for the last few decades. AONs are designed to inhibit the expression of a target RNA, or adjust the splicing pattern of an RNA. Scientists at ProQR have invented a new way to use oligonucleotides to edit single nucleotides in the RNA. These Editing Oligonucleotides (EONs) make specific A-to-I changes to RNA to reverse the underlying cause of currently untreatable diseases. We specifically design EONs that attract the cells own RNA editing machinery and direct it to a mutation site, where it repairs the RNA and thereby allows a functional protein to be produced. There are over 20,000 disease-causing G-to-A mutations that can potentially be targeted using this unique proprietary platform technology.
Endogenous systemADAR (Adenosine Deaminase Acting on RNA) is present in all human cells.
EON targetingEON (Editing Oligonucleotide) is designed to bind to the mRNA at the mutation site, creating a mismatch to expose the mutant A.
ADAR recruitmentFormation of the structure between the EON and the mRNA recruits ADAR to the target site.
ADAR functionA to I editing by ADAR performed at the specific location targeted by the EON. I is 'read' by translation machinery as G.
Applicability & potential
To target a specific disease, our EONs are designed to bind only to the specific, mutated site in the RNA. Special structures in the EON attract the endogenous ADAR complex to the site where the complex edits the targeted ‘A’ to an ‘I’. The EONs are short single stranded RNA molecules that are chemically modified to provide them with ideal drug-like properties for efficacy and uptake into cells. There are over 20,000 disease-causing mutations that can be ‘reversed’ by A to I editing. The vast majority of these diseases are currently untreatable.
In vivo proof of concept in disease modelWe have tested the technology in an in vivo model for Hurler syndrome. We designed an EON that successfully induced A to I editing of the mutated site in the IDUA RNA. This editing led to the restoration of iduronidase enzyme activity and reduced levels of the enzymes substrate (data presented in a Drug Information Association (DIA) webinar and at the 2017 Oligonucleotide Therapeutics Society (OTS) Meeting in Bordeaux, France) are available here.
Goals and strategy
We will further develop this platform through product and business development and plan to establish clinical proof of concept as soon as possible. The platform is uniquely positioned to target a wide range of diseases in a highly specific manner. Besides our own discovery efforts we are developing programs together with partners.