An official website of the United States government
The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before
sharing sensitive information, make sure you’re on a federal
government site.
The site is secure.
The https:// ensures that you are connecting to the
official website and that any information you provide is encrypted
and transmitted securely.
1 Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Genome Sciences, University of Washington, Seattle, WA, USA.
2 Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Genome Sciences, University of Washington, Seattle, WA, USA. Electronic address: ahberger@fredhutch.org.
1 Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Genome Sciences, University of Washington, Seattle, WA, USA.
2 Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Genome Sciences, University of Washington, Seattle, WA, USA. Electronic address: ahberger@fredhutch.org.
Cuella-Martin et al. (2021) and Hanna et al. (2021) showcase CRISPR base editing in large-scale pooled screens in human cells to discover both loss- and gain-of-function variants, enabling protein structure/function insights and clinical variant interpretation.
Figure 1.. Overview of CRISPR base editor screens.
(A) Two new studies perform CRISPR base…
Figure 1.. Overview of CRISPR base editor screens.
(A) Two new studies perform CRISPR base editor screens using a cytidine deaminase/Cas9 nickase base editor that generates C>T mutations in target genes. (B) The authors designed sgRNA libraries to generate mutations at target sites in genes of interest, which were introduced into haploid and diploid human cell lines along with the base editor in viability and drug screens. The functional effects of selected mutations were validated to provide insight into protein structure and function, and to predict whether the variants were benign or pathogenic in a clinical context. Figure created using BioRender.com.
Hanna RE, Hegde M, Fagre CR, DeWeirdt PC, Sangree AK, Szegletes Z, Griffith A, Feeley MN, Sanson KR, Baidi Y, Koblan LW, Liu DR, Neal JT, Doench JG.Hanna RE, et al.Cell. 2021 Feb 18;184(4):1064-1080.e20. doi: 10.1016/j.cell.2021.01.012.Cell. 2021.PMID: 33606977
Cuella-Martin R, Hayward SB, Fan X, Chen X, Huang JW, Taglialatela A, Leuzzi G, Zhao J, Rabadan R, Lu C, Shen Y, Ciccia A.Cuella-Martin R, et al.Cell. 2021 Feb 18;184(4):1081-1097.e19. doi: 10.1016/j.cell.2021.01.041.Cell. 2021.PMID: 33606978Free PMC article.
References
Berger AH, Brooks AN, Wu X, Shrestha Y, Chouinard C, Piccioni F, Bagul M, Kamburov A, Imielinski M, Hogstrom L, et al. (2016). High-throughput Phenotyping of Lung Cancer Somatic Mutations. Cancer Cell 30, 214–228.
-
PMC
-
PubMed
Cuella-Martin R, Hayward SB, Fan X, Chen X, Huang JW, Taglialatela A, Leuzzi G, Zhao J, Rabadan R, Lu C, Shen Y, and Ciccia A, (2020). Functional interrogation of genetic variants of the DNA damage response with CRISPR-dependent base editing screens. Cell.
-
PMC
-
PubMed
Després PC, Dubé AK, Seki M, Yachie N, and Landry CR (2020). Perturbing proteomes at single residue resolution using base editing. Nat. Commun 11, 1871.
-
PMC
-
PubMed
Findlay GM, Daza RM, Martin B, Zhang MD, Leith AP, Gasperini M, Janizek JD, Huang X, Starita LM, and Shendure J (2018). Accurate classification of BRCA1 variants with saturation genome editing. Nature 562, 217–222.
-
PMC
-
PubMed
Gaudelli NM, Komor AC, Rees HA, Packer MS, Badran AH, Bryson DI, and Liu DR (2017). Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature 551, 464–471.
-
PMC
-
PubMed