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Allen, Alexander G; Khan, Samia Q; Margulies, Carrie M; Viswanathan, Ramya; Lele, Swarali; Blaha, Laura; Scott, Sean N; Izzo, Kaitlyn M; Gerew, Alexandra; Pattali, Rithu; Cochran, Nadire R; Holland, Carl S; Zhao, Amy H; Sherman, Stephen E; Jaskolka, Michael C; Wu, Meng; Wilson, Aaron C; Sun, Xiaoqi; Ciulla, Dawn M; Zhang, Deric; Nelson, Jacqueline D; Zhang, Peisheng; Mazzucato, Patrizia; Huang, Yan; Giannoukos, Georgia; Marco, Eugenio; Nehil, Michael; Follit, John A; Chang, Kai-Hsin; Shearman, Mark S; Wilson, Christopher J; Zuris, John A
Nature biotechnology, 03/2024, Letnik: 42, Številka: 3Journal Article
Inefficient knock-in of transgene cargos limits the potential of cell-based medicines. In this study, we used a CRISPR nuclease that targets a site within an exon of an essential gene and designed a cargo template so that correct knock-in would retain essential gene function while also integrating the transgene(s) of interest. Cells with non-productive insertions and deletions would undergo negative selection. This technology, called SLEEK (SeLection by Essential-gene Exon Knock-in), achieved knock-in efficiencies of more than 90% in clinically relevant cell types without impacting long-term viability or expansion. SLEEK knock-in rates in T cells are more efficient than state-of-the-art TRAC knock-in with AAV6 and surpass more than 90% efficiency even with non-viral DNA cargos. As a clinical application, natural killer cells generated from induced pluripotent stem cells containing SLEEK knock-in of CD16 and mbIL-15 show substantially improved tumor killing and persistence in vivo.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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