Adenosine deaminase acting on RNA (ADAR) complexed with target mRNA via OPERA oligonucleotide (ADAR-mRNA-OPERA)

The endogenous ADAR enzyme complexed with target mRNA via an OPERA (Oligonucleotide-mediated Programmable Editing of RNA) oligonucleotide is a therapeutic assembly designed for precision RNA editing (Reautschnig et al., 2022) [2]. ADAR (Adenosine Deaminase Acting on RNA) is a naturally occurring enzyme that catalyzes the deamination of adenosine to inosine within double-stranded RNA regions (Mizrahi et al., 2021) [3]. The OPERA platform utilizes synthetic antisense oligonucleotides to recruit these endogenous ADAR enzymes to specific sequences on a target mRNA transcript (Vogel et al., 2018) [4]. Once recruited, the ADAR enzyme performs a site-specific A-to-I conversion, which is interpreted as a guanosine (G) by the cellular translation machinery (ProQR Therapeutics, 2023) [1]. This mechanism allows for the correction of pathogenic G-to-A mutations or the modulation of protein function without the need for permanent DNA alteration. This technology is currently being explored for the treatment of various genetic conditions, including Alpha-1 antitrypsin deficiency and inherited retinal diseases (Reautschnig et al., 2022) [2]. By leveraging the cell's own editing machinery, this approach minimizes the risks of immunogenicity and off-target effects associated with exogenous CRISPR-Cas systems.

Other names

OPERA RNA editing platformADAR-recruiting oligonucleotide complexA-to-I RNA editing complexAxiomer RNA editing technologyOligonucleotide-mediated Programmable Editing of RNA

Recruitment of endogenous ADAR to catalyze site-specific adenosine-to-inosine (A-to-I) conversion in mRNA, which is read as guanosine (G) by the ribosome.