Professor Makoto Takeda will present a light-controlled, temperature-sensitive Sendai virus vector at the Annual Meeting of the Japanese Society for Regenerative Medicine.

The 25th Annual Meeting of the Japanese Society for Regenerative Medicine
March 19–20, 2026
Kobe International Conference Center, Kobe, Japan

https://site.convention.co.jp/jsrm2026/

A Light-Controlled Temperature-Sensitive Sendai Virus Vector Enables High-Level Expression and On-Demand Elimination of the Viral Vector

Makoto Takeda¹, Takashi Okura², Maino Tahara², Mika Hosoki¹, Hiroshi Katoh¹, Moritoshi Sato³⁴

¹ Graduate School of Medicine and Faculty of Medicine, The University of Tokyo
² National Institute of Infectious Diseases, Japan Institute for Health Security
³ Graduate School of Arts and Sciences, The University of Tokyo
⁴ Kanagawa Institute of Industrial Science and Technology

Virus vectors based on recombinant viral technologies remain important tools in gene therapy and regenerative medicine. We have long worked on the development of mononegavirus-based vectors primarily intended for ex vivoapplications. Among mononegavirus vectors, the Sendai virus vector is widely used in the field of regenerative medicine.

We previously developed light-responsive viral vectors using multiple mononegaviruses, including measles virus, rabies virus, vesicular stomatitis virus, and bovine parainfluenza virus type 3, in which gene expression can be precisely controlled by blue-light irradiation. Here, we report the successful introduction of the same strategy into Sendai virus.

As in our previous optogenetic viral vectors, the light-responsive molecule Magnet, which changes its dimerization state in a blue-light-dependent manner, was inserted into the linker region between the connector domain and the methyltransferase domain of the L protein, the RNA-dependent RNA polymerase of mononegaviruses. A recombinant Sendai virus carrying this modification was then generated.

Although the recombinant Sendai virus exhibited slower growth kinetics, its final viral titer reached a level comparable to that of wild-type Sendai virus. The recombinant virus efficiently mediated gene expression under blue-light irradiation, whereas its activity was markedly reduced in the dark. In addition, the virus displayed temperature sensitivity: high gene expression was observed at 33 °C, while expression was markedly suppressed at 37 °C. Thus, high expression was obtained under 33 °C with blue-light illumination, whereas placing the cells at 37 °C in the dark suppressed expression below the detection limit, demonstrating intentional and rapid elimination of the viral vector.

These results indicate that this recombinant Sendai virus may become a promising tool for future applications in regenerative medicine.