2026-06-17 東京大学

CRISPR KO マウスライブラリによる生体内スクリーニング:84系統から17個の抵抗性遺伝子を発見
<関連情報>
- https://www.u-tokyo.ac.jp/focus/ja/press/z0406_00010.html
- https://www.cell.com/cell/abstract/S0092-8674(26)00591-X
インフルエンザ研究における機能ゲノミクスのためのCRISPRノックアウトマウスライブラリー A CRISPR knockout mouse library for functional genomics in influenza research
Hiroshi Ueki ∙ Yuriko Tomita ∙ Calvin Duong ∙ … ∙ Nobuaki Yoshida ∙ Tokiko Watanabe ∙ Yoshihiro Kawaoka
Cell Published:June 16, 2026
DOI:https://doi.org/10.1016/j.cell.2026.05.032
Highlights
- We generated a CRISPR-Cas9 library of 84 mouse lines for in vivo influenza study
- We found 17 gene modifications that confer resistance to influenza virus infection
- RGNEF ablation protects mice by suppressing viral replication in the lung
- LASP1 modification protects mice via virus replication-independent mechanisms
Summary
Functional validation of host factors in whole-animal models is a major bottleneck in virology; it hinders the translation of data from in vitro studies into a deeper understanding of the viral life cycle and pathogenesis. To address this challenge, we developed a systematic in vivo screening platform for influenza A virus. This platform comprises a library of 84 CRISPR-Cas9-generated gene-modified mouse lines targeting host factors prioritized from the literature and in vitro small interfering RNA (siRNA) screening studies. Using this resource, we identified 17 host factors whose genetic ablation conferred resistance to influenza A virus infection. Further studies of two of these factors, Arhgef28 and Lasp1, revealed distinct protective mechanisms against influenza A virus. We offer this mouse library to the research community as a powerful platform for studying virus-host interactions in a physiologically relevant context.

