Golden Gate Assembly of CRISPR gRNA expression array for simultaneously targeting multiple genes

Cell Mol Life Sci. 2016 Nov;73(22):4315-4325. doi: 10.1007/s00018-016-2271-5. Epub 2016 May 13.

Abstract

The engineered CRISPR/Cas9 technology has developed as the most efficient and broadly used genome editing tool. However, simultaneously targeting multiple genes (or genomic loci) in the same individual cells using CRISPR/Cas9 remain one technical challenge. In this article, we have developed a Golden Gate Assembly method for the generation of CRISPR gRNA expression arrays, thus enabling simultaneous gene targeting. Using this method, the generation of CRISPR gRNA expression array can be accomplished in 2 weeks, and contains up to 30 gRNA expression cassettes. We demonstrated in the study that simultaneously targeting 10 genomic loci or simultaneously inhibition of multiple endogenous genes could be achieved using the multiplexed gRNA expression array vector in human cells. The complete set of plasmids is available through the non-profit plasmid repository Addgene.

Keywords: CRISPR; Cas9; Genome editing; Golden Gate Assembly; Simultaneous multiple gene inhibition; Simultaneous multiple gene knockout.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cloning, Molecular
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics*
  • Fluorescent Dyes / metabolism
  • Gene Deletion
  • Gene Expression*
  • Gene Targeting / methods*
  • Gene Transfer Techniques
  • Genes, Reporter
  • Genetic Loci
  • Humans
  • Plasmids / metabolism
  • Polymerase Chain Reaction
  • RNA, Guide, CRISPR-Cas Systems / genetics*
  • Reproducibility of Results

Substances

  • Fluorescent Dyes
  • RNA, Guide, CRISPR-Cas Systems