An antisense oligonucleotide (ASO) is a short synthetic fragment of DNA or RNA designed in the laboratory to bind specifically to a complementary sequence of messenger RNA (mRNA) in a cell. The process of designing antisense oligonucleotides in silico is often long and tedious. Florian Malard (post-doc ARNA, Campagne Team, IECB), Eric Roubin (head of IT, UAR3033 US001 IECB) and their colleagues have developed a tool called AntiSense Oligonucleotide Generator (ASOG) to make this process faster, simpler, and more reliable. This research may be useful to anyone involved in the design of antisense oligonucleotides for both fundamental and therapeutic applications (Kimi et al, 2025, Computational and Structural Biotechnology Journal).

• Can you introduce yourselves in one sentence? What was your contribution to this project ?

Eric Roubin (IT Manager, UAR3033 US001 IECB): I contributed my expertise in setting up a secure IT infrastructure tailored to the project's needs. This enabled ASOG to be developed under favorable conditions. I was particularly motivated by this project because it is a real opportunity to contribute to science by putting the necessary technical tools in place. It allows us to provide concrete help to science.

Florian Malard (postdoctoral researcher, ARNA unit): I contributed to the project by coordinating all the work of the collaborators and by being directly involved in the development of the application. Among the partners, there is in particular Jonah Kimi, a brilliant master's student, who did most of the development in record time. Patricia Korczak and Brune Vialet, researchers at the ARNA laboratory, provided us with extensive guidance during development, as they were the operators on whose basis we designed the application model. This project was funded by the ARNA internal call for projects and thanks to the support of Philippe Barthélémy and Sébastien Campagne, who placed their trust in me to see it through.

• Why is this topic important today ?

Antisense oligonucleotides are classified as RNA-based therapies. These emerging modalities target RNA metabolism to offer new avenues for treating previously incurable diseases. It is now possible to target the RNA encoding these proteins using an antisense oligonucleotide, which hybridizes complementarily to induce a biological effect.

• What does your study add to what we already knew ?

A number of programs facilitating the design of antisense oligonucleotides were already available. The specificity of ASOG lies in its generalist approach and its goal of providing the necessary elements for decision-making, rather than making a choice on behalf of the user.

•  What were the main difficulties or limitations encountered ?

Eric: The main difficulty was setting up a secure web server isolated from the local network to avoid any risk of hacking or unauthorized access to the site's data.

Florian: This type of project requires significant expertise in both biology and computer science. The main risk when developing such an application is ending up with a product that is functional but difficult to upgrade: computer code requires structure, rigor, and compliance with numerous conventions. I was fortunate to work with Jonah Kimi (Master's 1), who did most of the application development. We made a significant effort to follow a development model that now allows us to consider ASOG as a long-term, modular, and scalable project. The main challenge was therefore to develop a functional web application in a short period of time (two months), while meeting these requirements and aiming for sustainable development. Today, the main limitation of ASOG is the absence of certain annotations on the sequences processed. In the future, we plan to integrate data from the international ENCyclopedia Of DNA Elements (ENCODE, https://www.encodeproject.org/) project in order to be able to select more precisely the regions of interest to target, in particular the binding sites of splicing factors.

• Who might be directly concerned by these results ?

The first people affected by these results are technicians, engineers, and researchers who want to design antisense oligonucleotides using a methodology compatible with the one we propose. This work is of interest to both academia and industry. In collaboration with Inserm Transfert, the start-up NAXIA Discovery, for example, uses this software and has participated in the development of an improved version that will soon be available online.

• What concrete changes will these results bring about ?

A task that previously took operators several days to complete can now be done in 10 minutes thanks to ASOG. This procedure, which used to be long, tedious, and repetitive, is now fast, automated, and optimized. This benefits the operator and reduces the risk of error.

• What are the possible applications (short- or long-term) of this research ?

Available since June 2025, ASOG is already used by more than 300 registered users worldwide, for more than 1,000 completed antisense oligonucleotide design processes. In the longer term, we want to continue developing ASOG to make antisense oligonucleotide design even faster and more effective in terms of biological effects.

• What are the key findings for someone who won't read the scientific article ?

The computational approach we propose, in the form of a web-based tool, requires only a target sequence as input. ASOG thus gathers the information you need to choose the antisense oligonucleotides to be tested experimentally. It performs these analyses in a matter of minutes, freeing up the time you need to make a more informed decision. ASOG's motto is: “Search quickly, decide wisely.” "

• How can I access ASOG ? What's new since publication ?

ASOG is available to the community at https://asog.iecb.u-bordeaux.fr.

Since the original publication, we have recruited Pierre Laporte, a master's student, who has developed a module dedicated to the design of antisense oligonucleotides for exon skipping, among other improvements. Several of these implementations will soon be online, including: transcript search via the Ensembl database, implementation of ViennaRNA engines in addition to MFold, a JobMerger to identify compatible sequences between species, and many other features to come, we hope.

• If you had to summarize your article in a sentence that a non-specialist could understand, what would you say ?

ASOG makes it possible to quickly and easily obtain numerous physicochemical and biological properties associated with dozens, even hundreds, of candidate antisense oligonucleotides. This saves a significant amount of time, allowing scientists to focus on decision-making rather than searching for information.