Targeted RNA Adenosine (RNA-A)

Targeted RNA adenosines refer to specific nucleotide residues within messenger RNA (mRNA) transcripts that are selected for site-specific modification to treat genetic diseases. This therapeutic approach utilizes engineered oligonucleotides, such as Wave Life Sciences' AIMers or ProQR's Axiomer guides, to recruit endogenous Adenosine Deaminase Acting on RNA (ADAR) enzymes to a precise location (1.1.1, 1.1.2). The enzyme catalyzes the deamination of the target adenosine into inosine, which the cellular translation machinery subsequently interprets as guanosine (1.1.2). This "A-to-I" editing allows for the correction of pathogenic G-to-A point mutations or the modulation of protein function without making permanent, irreversible changes to the genome (1.1.3). The most advanced application of this technology is WVE-006, which targets the SERPINA1 transcript to restore functional alpha-1 antitrypsin protein in patients with Alpha-1 antitrypsin deficiency (1.1.4, 1.1.5).

Other names

Specific RNA adenosines within designed target transcriptsRNA editing siteTargeted adenosineA-to-I editing siteADAR target siteSite-specific RNA adenosine

Site-specific A-to-I RNA editing via recruitment of endogenous Adenosine Deaminase Acting on RNA (ADAR) enzymes to convert a targeted adenosine to inosine, which is read as guanosine by the translation machinery.