Nature biomedical engineeringJul 16, 2026

Using RModBlock antisense oligonucleotides to precisely and efficiently block RNA modifications

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 17, 2026

Abstract

RModBlock ASOs inhibited RNA modifications by up to 97% in human cells.

The RNA Modification-Blocking strategy uses chemically modified antisense oligonucleotides to prevent specific RNA modifications.
RModBlock ASOs effectively blocked the formation of structural contexts necessary for certain modifications, such as m⁵C and pseudouridine.
The approach demonstrated broad applicability by also inhibiting m⁶A despite it not requiring strict structural contexts.
RModBlock ASOs showed comparable or superior effectiveness compared to existing dCas13-eraser-based systems.
Inhibition of cancer-related RNA modifications was achieved, indicating potential therapeutic uses.
The strategy is presented as a precise, efficient method for manipulating RNA modifications in both basic and translational research.

Simplified

The ability to selectively edit specific RNA modifications is needed to understand their roles in cellular function and disease. However, existing approaches, particularly catalytically inactive Cas (dCas)-based systems, have limited applicability owing to their reliance on eraser proteins, and their performance can vary depending on the modification type and target context. Here we introduce the RNA Modification-Blocking (RModBlock) strategy, which uses chemically modified antisense oligonucleotides (ASOs) with locked nucleic acid to precisely inhibit modifications at targeted sites. Most RNA modification writers, including those for m⁵C and pseudouridine, require specific structural contexts. Using representative modifications with and without eraser proteins, m⁵C and pseudouridine, respectively, we demonstrated that RModBlock ASOs blocked the formation of their structural context, inhibiting modified bases by up to 97% in human cells. RModBlock ASOs also inhibited m⁶A, despite its writer protein not requiring a strict structural context, suggesting broad applicability. Moreover, this strategy achieves comparable or superior performance when dCas13-eraser-based systems are applicable. Finally, by inhibiting cancer-relevant modifications and through in vivo delivery to the mouse liver, we highlight its therapeutic potential. This showcases the RModBlock strategy as a precise, efficient and versatile approach for manipulating RNA modifications, with broad applicability in basic and translational research.

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

Competing Interests: R.Z., M.M., J.Y. and K.K. are inventors of filed patents based on the work published here. The other authors declare no competing interests.

PubMed

Using RModBlock antisense oligonucleotides to precisely and efficiently block RNA modifications

Abstract

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the mrna technology brief