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Generation and validation of CRISPR-engineered human natural killer cell lines for research and therapeutic applications

Cytotoxic natural killer cells kill tumors and infected cells. We carried out CRISPR-based gene editing and transcriptional regulation in hard-to-manipulate NK-92 cells. NK-92-based therapies were found to be safe and efficacious in preclinical studies of cancers. Here, we have pioneered the generat...

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Detalles Bibliográficos
Autores principales: Kumar, Anil, Lee, Sung June, Liu, Qiao, Chan, Anthony K.N., Pokharel, Sheela Pangeni, Yu, Jianhua, Chen, Chun-Wei, Swaminathan, Srividya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551845/
https://www.ncbi.nlm.nih.gov/pubmed/34746857
http://dx.doi.org/10.1016/j.xpro.2021.100874
Descripción
Sumario:Cytotoxic natural killer cells kill tumors and infected cells. We carried out CRISPR-based gene editing and transcriptional regulation in hard-to-manipulate NK-92 cells. NK-92-based therapies were found to be safe and efficacious in preclinical studies of cancers. Here, we have pioneered the generation and validation of NK-92 cells constitutively expressing Cas9 or dCas9 for knockout (CRISPRko), transcriptional activation (CRISPRa), or transcriptional repression (CRISPRi) of genes. Our CRISPR-engineered NK-92 cell platforms can be modified for research and off-the-shelf therapeutic applications.