Scientists at ProQR have invented a new way to use RNA oligonucleotides to alter RNA. The Axiomer RNA editing technology enables the editing of specific single nucleotides in RNA. This technology could reverse the underlying cause of currently untreatable diseases.
Our Axiomer technology enables your body to repair its own RNA.
A new way to design oligonucleotide therapies
A new way to design oligonucleotide therapies
Antisense oligonucleotides (AONs) have been used as therapeutics for the last few decades. ProQR has built an extensive pipeline of investigational RNA therapies based on the technologies already available. But our scientists have gone beyond that and invented an entirely new way of using oligonucleotides for the treatment of genetic diseases. These Editing Oligonucleotides (EONs) make specific single nucleotide edits to RNA to reverse a mutation.
Endogenous system
Over 20.000 diseases are caused by G to A mutations.
EON targeting
EON (Editing Oligonucleotide) is designed to bind the mRNA at the mutation site, creating a mismatch to expose the mutant A.
ADAR recruitment
ADAR (Adenosine denaminase acting on RNA) is present in all human cells, and the formation of the structure between the EON and the mRNA recruits ADAR to the target site.
ADAR function
A to I editing by ADAR performed at the specific location targeted by the EON. I is "read" by translation machinery as G.
The Axiomer platform
The Axiomer platform
Using the Axiomer technology, we specifically design our EONs to recruit the cell’s own RNA editing machinery. This is a protein called ADAR (which stands for adenosine deaminase acting on RNA) and is used by human cells to make adenine (A) to inosine (I) changes in RNA. An ‘I’ in RNA is read by the translation machinery as a guanine (G). In short, we can design EONs to direct the cell to repair its own RNA with ADAR.
Applicability & potential
Applicability & potential
To target a specific disease, our EONs are designed to bind only to the specific, mutated site in the RNA. Special structures formed together with the RNA and the EON attract the endogenous ADAR so it 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 model
In vivo proof of concept in disease model
We have tested the technology in an in vivo model for Hurler syndrome. We designed an EON to induce A-to-I editing of the mutated site in the Idua RNA. Using only this EON as single-component treatment, we were able to show that the ADAR naturally present in the cells was recruited to the mutated site and edited it.
Goals and strategy
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.
Meet Bart Klein - Senior Vice President Innovation
"Axiomer opens up a whole new way of designing medicines"
Read the interview