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DNA-Tethered RNA Polymerase for Programmable In vitro Transcription and Molecular Computation

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ASOG: AntiSense Oligonucleotide Generator.

Jonah Kimi^1,2, Patricia Korczak¹, Brune Vialet¹

¹Univ. Bordeaux, CNRS, INSERM, ARNA UMR 5320, U1212, F-33000 Bordeaux, France.

Computational and Structural Biotechnology Journal

|October 6, 2025

Summary

We developed the AntiSense Oligonucleotide Generator (ASOG), a web application for designing antisense oligonucleotides (ASOs). ASOG streamlines ASO design by predicting properties, masking splice sites, and detecting off-target effects.

Keywords:

Antisense oligonucleotide BLASTn Melting temperature calculation Splice site prediction Webserver

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Area of Science:

Molecular Biology
Bioinformatics
Computational Biology

Background:

Antisense oligonucleotides (ASOs) are crucial for modulating gene expression in research and clinics.
Manual ASO design is time-consuming, limiting exploration of the ASO design space.
Existing automated ASO design tools have limitations, necessitating new approaches.

Purpose of the Study:

To introduce a generalistic and original pipeline for automated antisense oligonucleotide (ASO) design.
To provide a user-friendly web application, ASOG, for efficient ASO exploration.
To facilitate informed decision-making in ASO selection for research and therapeutic applications.

Main Methods:

Development of a web application, AntiSense Oligonucleotide Generator (ASOG), integrating explicit criteria, original algorithms, and third-party software.
ASOG pipeline accepts a target gene sequence for comprehensive ASO analysis.
Prediction of ASO structural properties, splice site masking, off-target effects, and thermodynamic hybridization parameters, including RNA modifications.

Main Results:

ASOG enables rapid generation and evaluation of antisense oligonucleotides (ASOs).
The pipeline predicts key parameters essential for ASO efficacy and specificity.
It accounts for common RNA modifications, enhancing prediction accuracy.

Conclusions:

ASOG offers a versatile and efficient solution for navigating the antisense oligonucleotide design space.
The webserver empowers researchers to quickly identify optimal ASOs for their applications.
ASOG represents a significant advancement in facilitating ASO-based gene modulation strategies.