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Precise Cas9 targeting enables genomic mutation prevention

2018; National Academy of Sciences; Volume: 115; Issue: 14 Linguagem: Inglês

10.1073/pnas.1718148115

1091-6490

Alejandro Chavez, Benjamin W. Pruitt, Marcelle Tuttle, Rebecca S. Shapiro, Ryan J. Cecchi, Jordan Winston, Brian M. Turczyk, Michael Tung, James J. Collins, George M. Church,

Pluripotent Stem Cells Research

Significance Single-base substitutions are capable of producing transformative phenotypic changes. While methods to classify such mutations are well established, it is difficult to modulate or preclude their occurrence in a direct and efficacious manner. In this study, we refine the specificity of the CRISPR-Cas9 system and present a general framework for proactively preventing the occurrence of point mutations. This “mutation prevention system” is a broadly useful tool for the study and control of DNA substitutions, particularly in contexts where an associated phenotype or evolutionary pathway is undesirable.