Secure, fast in silico analysis with no missed hits.

Chemicals Evaluation and Research Institute, Japan (CERI).

When launching its contract testing service for evaluating off-target effects of oligonucleotide therapeutics, the Chemicals Evaluation and Research Institute, Japan adopted Retrieva’s GGGenome packaged version for the in silico analysis offered as part of that service. Because it runs offline, it safeguards client information including nucleotide sequences, and supports in silico analysis that is fast and misses no hits.

Why the GGGenome packaged version

Japan’s first service for evaluating off-target effects of oligonucleotide therapeutics

The Chemicals Evaluation and Research Institute, Japan (CERI) conducts testing, inspection, evaluation and research and development on chemical substances. Its purpose is to improve the quality of chemical substances and ensure their safety while protecting the environment and public health, thereby contributing to the sound development of industry and to better living standards.

A defining characteristic of our institute is that we are a fair and neutral third party. Working on commission from clients, our skilled technical staff carry out testing, inspection, research and investigation across the whole field of chemical substance evaluation.

Kazuya Ishida, Deputy Manager, First Research Section, First Research Department, Safety Assessment Technology Research Institute

From that neutral position, CERI provides a range of solutions for evaluating and managing chemical substances and chemical products. One of them is testing and evaluation of pharmaceuticals (small molecule and biologic), pharmaceutical impurities and medical devices, covering microbiological testing, evaluation of medical materials and various safety tests. Evaluating off-target effects of oligonucleotide therapeutics is one such service, carried out on commission from pharmaceutical companies. CERI says it was the first CRO (contract research organization) in Japan to offer off-target effect evaluation for oligonucleotide therapeutics as a service.

Adopted for data security and ease of search

Oligonucleotide therapeutics are drawing considerable attention as a new modality, and the market is expanding; 2020 saw the first oligonucleotide therapeutic from a Japanese company reach the market. "Development of oligonucleotide therapeutics is picking up at domestic pharmaceutical companies as well, so I expect the number to grow further," says Koji Jojima of the First Research Section, First Research Department, Safety Assessment Technology Research Institute at CERI.

Oligonucleotide therapeutics have effects that conventional drugs do not, and direct effects on non-target genes — off-target effects — must be evaluated to ensure safety. CERI performs this evaluation using in silico analysis based on human genomic DNA and RNA information, together with in vitro microarray analysis using human cells.

While considering tools for in silico analysis as it launched the service, CERI heard at the annual meeting of the Japan Society of Nucleic Acid Therapeutics that Retrieva offered the GGGenome packaged version, fast nucleotide sequence search software, and decided to adopt it. The GGGenome packaged version is a packaged solution that performs the same nucleotide sequence searches as the GGGenome web edition provided by the Database Center for Life Science (DBCLS) of the Joint Support-Center for Data Science Research, Research Organization of Information and Systems, on computers inside the user’s own organization.

The in silico analysis for evaluating off-target effects involves selecting the search database and the search algorithm, and the GGGenome packaged version is used for this.

When pharmaceutical companies commission work from us, they ask that confidential information about compounds under development not go online, so a packaged version that can search in a closed environment is essential. While gathering information on various tools we also spoke with Yuki Naito, the Project Assistant Professor at DBCLS who developed the GGGenome web edition. He gave us a great deal of useful insight — including that GGGenome suits searching short sequences such as those of oligonucleotide therapeutics — and we decided to adopt it.

Kazuya Ishida

The GGGenome packaged version connects to any terminal by USB and runs on that terminal, so no data goes online and query sequences remain confidential.

Beyond offline use, Jojima points to ease of search, rating the packaged version highly: "Compared with other tools, exhaustive searches are simple to run."

Expanding the off-target evaluation service further

CERI adopted the packaged version formally after verifying it — including database updates — together with Retrieva and Professor Naito. During the rollout, Retrieva supported CERI on any open questions, the deployment completed without trouble, and the off-target evaluation service launched officially. CERI has also added optional databases in order to meet a wide range of client needs.

With client numbers rising year on year since the service began, CERI is now working to make the evaluation process as a whole more efficient and faster.

Used well, features such as gene-of-interest highlighting — which compares a prepared gene list against GGGenome search results and highlights the hits — and the search support script (Bioret tool) for searching multiple sequences at once should bring substantial gains in efficiency and speed.

Koji Jojima, First Research Section, First Research Department, Safety Assessment Technology Research Institute

After the 2020 edition, CERI also adopted the 2021 edition of the GGGenome packaged version, and plans to continue with the 2022 edition. It intends to keep expanding the off-target evaluation service. "We expect demand for contract testing of off-target effects to grow," Ishida says of the outlook. "Among the several types of oligonucleotide therapeutics, we currently focus on antisense oligonucleotides and siRNA, but we want to deepen our knowledge of miRNA as well and expand into that."

Other case studies and interviews

Yuki Naito, Project Assistant Professor / DBCLS

We interviewed Yuki Naito, the Project Assistant Professor at DBCLS who developed GGGenome, about the background to its development and what it may mean for the future of life science research.

PtBio Inc.

The GGGenome packaged version powers the safety assessment feature offered in their open platform for genome editing support.

National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN)

The GGGenome packaged version is used to assess off-target risk for antisense oligonucleotides in their artificial nucleic acid screening project.