The rapidly advancing field of molecular medicine has seen a promising breakthrough with the development of two groundbreaking techniques in genome editing and CAR-T cell therapy. Research conducted by a team from Kyushu University has revealed new insights into how to overcome challenges associated with CAR-T cell therapy, specifically in predicting the risks of neurotoxicity.

On March 21, 2025, the team, led by Professor Yuuya Kunisaki of Kyushu University's Graduate School of Medical Sciences, announced the successful identification of a biomarker that can predict the onset of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) prior to treatment. This neurotoxicity is a significant side effect of CAR-T therapy, which although effective, can lead to serious neurological complications.

"By leveraging the mass spectrometry platform established in our clinical laboratory, we were able to capture changes in the combinations of trace proteins," stated Professor Kunisaki. The research indicates potential routine biochemical tests and the development of simple test kits to enhance patient safety during CAR-T cell therapy.

Moreover, the team is investigating the possibility of using complement-targeting drugs that could help prevent or treat ICANS. Professor Kunisaki expressed hope that these drugs could pave the way for further advancements in preventive and therapeutic approaches for managing the side effects of CAR-T therapy. This research is expected to have practical applications in clinical settings.

In a separate yet equally notable development, the same day researchers at Kyushu University also unveiled an innovative genome editing technique known as BITREx. The new method was designed to significantly amplify genes' presence on the genome through an experimental evolutionary process.

Professor Hiroaki Takei and his colleagues, including Associate Professors Satoshi Okada and Takashi Ito, developed BITREx to enhance gene amplification using a mutant variant of the Cas9 protein, referred to as nCas9. By disrupting the replication fork—a critical site for DNA replication—the technique allows for extensive elongation of clustered gene arrays, which may have far-reaching implications for research and therapeutic applications.

During their research, the team utilized budding yeast as a model organism to explore BITREx’s capabilities. Remarkably, they managed to extend an array within a 2,000-base-pair repeat unit to roughly 500 iterations, collectively encompassing approximately one million base pairs. These findings mark a significant leap in the field of genome editing, as achieving such levels of amplification was previously unfeasible.

The potential applications of BITREx are vast, ranging from experimental evolution and production of useful substances to gene therapy. Even more exciting, the researchers found success in human cultured cells, effectively extending gene arrays using BITREx techniques.

"A few years ago, we discovered that a Cas9 variant that does not cause complete DNA breaks could obstruct the progress of the replication fork. Since then, we have been working on inducing large genomic structural changes based on this new concept," remarked Professor Ito. He expressed optimism regarding BITREx's potential, indicating that it may contribute to understanding diseases caused by shortened gene arrays.

Both advancements from Kyushu University are expected to appear in the United States journal Cell Genomics on the same date, March 21, 2025, showcasing the university's role in leading innovative research in the field of molecular biology. As researchers continue to unveil new methodologies, the hope is that such progress will significantly impact treatments available in both clinical and research settings.