Cellular RNA substrates incidentally edited by TadA*7.10 (ABE7.10 RNA off-targets)

Cellular RNA substrates incidentally edited by TadA*7.10 refer to the vast array of messenger RNA (mRNA) and other RNA transcripts that undergo unintended adenosine-to-inosine (A-to-I) deamination when the Adenine Base Editor 7.10 (ABE7.10) is present in a cell (Grünewald et al., 2019, Nature). TadA*7.10 is an evolved version of the Escherichia coli tRNA adenosine deaminase enzyme, engineered to edit DNA but retaining a high affinity for RNA (Gaudelli et al., 2017, Nature). Research has shown that ABE7.10 can cause thousands of off-target RNA edits across the transcriptome, which are independent of the DNA-targeting guide RNA (Zhou et al., 2019, Nature). These incidental edits can lead to the translation of mutant proteins or altered RNA stability, posing a significant safety concern for the clinical application of base editing technologies. While newer generations of base editors, such as ABE8e or SECURE-ABEs, have been developed to minimize these effects, the RNA substrates of TadA*7.10 remain a critical benchmark for evaluating the specificity and safety of genome editing tools. Monitoring these substrates is essential for ensuring that therapeutic base editing does not induce systemic proteomic instability or unintended phenotypic changes.

Other names

Transcriptome-wide RNA off-targets of ABE7.10TadA*7.10-mediated RNA editingABE-induced RNA deaminationIncidental RNA substrates of adenine base editors

The TadA*7.10 subunit of the ABE7.10 base editor catalyzes the hydrolytic deamination of adenosine to inosine (A-to-I) in cellular RNA transcripts, which are then interpreted as guanosine by the translation machinery (Grünewald et al., 2019; Zhou et al., 2019).