tetano
Editor, Senior Moderator
Cell
. 2026 Jun 16:S0092-8674(26)00591-X.
doi: 10.1016/j.cell.2026.05.032. Online ahead of print.
A CRISPR knockout mouse library for functional genomics in influenza research
Hiroshi Ueki[SUP] 1 [/SUP], Yuriko Tomita[SUP] 2 [/SUP], Calvin Duong[SUP] 3 [/SUP], Hiromichi Mitake[SUP] 3 [/SUP], Maki Kiso[SUP] 4 [/SUP], Yuri Furusawa[SUP] 5 [/SUP], Dongming Zhao[SUP] 3 [/SUP], Tiago Jose da Silva Lopes[SUP] 6 [/SUP], Li Wu[SUP] 3 [/SUP], Huapeng Feng[SUP] 3 [/SUP], Seiya Yamayoshi[SUP] 1 [/SUP], Satoshi Fukuyama[SUP] 3 [/SUP], Makoto Yamashita[SUP] 3 [/SUP], Manabu Ozawa[SUP] 7 [/SUP], Masahito Ikawa[SUP] 8 [/SUP], Nobuaki Yoshida[SUP] 9 [/SUP], Tokiko Watanabe[SUP] 10 [/SUP], Yoshihiro Kawaoka[SUP] 11 [/SUP]
Affiliations
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.
Keywords: CRISPR-Cas9; LASP1; RGNEF; antiviral targets; host factors; host-directed therapy; in vivo model; influenza A virus.
. 2026 Jun 16:S0092-8674(26)00591-X.
doi: 10.1016/j.cell.2026.05.032. Online ahead of print.
A CRISPR knockout mouse library for functional genomics in influenza research
Hiroshi Ueki[SUP] 1 [/SUP], Yuriko Tomita[SUP] 2 [/SUP], Calvin Duong[SUP] 3 [/SUP], Hiromichi Mitake[SUP] 3 [/SUP], Maki Kiso[SUP] 4 [/SUP], Yuri Furusawa[SUP] 5 [/SUP], Dongming Zhao[SUP] 3 [/SUP], Tiago Jose da Silva Lopes[SUP] 6 [/SUP], Li Wu[SUP] 3 [/SUP], Huapeng Feng[SUP] 3 [/SUP], Seiya Yamayoshi[SUP] 1 [/SUP], Satoshi Fukuyama[SUP] 3 [/SUP], Makoto Yamashita[SUP] 3 [/SUP], Manabu Ozawa[SUP] 7 [/SUP], Masahito Ikawa[SUP] 8 [/SUP], Nobuaki Yoshida[SUP] 9 [/SUP], Tokiko Watanabe[SUP] 10 [/SUP], Yoshihiro Kawaoka[SUP] 11 [/SUP]
Affiliations
- PMID: 42302780
- DOI: 10.1016/j.cell.2026.05.032
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.
Keywords: CRISPR-Cas9; LASP1; RGNEF; antiviral targets; host factors; host-directed therapy; in vivo model; influenza A virus.