Endogenous Fluorescence Tagging by CRISPR

Trends Cell Biol. 2019 Nov;29(11):912-928. doi: 10.1016/j.tcb.2019.08.004. Epub 2019 Sep 12.

Abstract

Fluorescent proteins have revolutionized biomedical research as they are easy to use for protein tagging, cope without fixation or permeabilization, and thus, enable live cell imaging in various models. Current methods allow easy and quick integration of fluorescent markers to endogenous genes of interest. In this review, we introduce the three central methods, zinc finger nucleases (ZFNs), transcription activator-like effectors (TALENs), and CRISPR, that have been widely used to manipulate cells or organisms. Focusing on CRISPR technology, we give an overview on homology-directed repair (HDR)-, microhomology-mediated end joining (MMEJ)-, and nonhomologous end joining (NHEJ)-based strategies for the knock-in of markers, figure out recent developments of the technique for highly efficient knock-in, and demonstrate pros and cons. We highlight the unique aspects of fluorescent protein knock-ins and pinpoint specific improvements and perspectives, like the combination of editing with stem cell derived organoid development.

Keywords: CRISPR; DNA double-strand breaks; DNA repair; GFP knock-in; gene editing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CRISPR-Cas Systems / genetics*
  • Caenorhabditis elegans / genetics
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics
  • DNA / genetics
  • DNA End-Joining Repair / genetics
  • Fluorescence
  • Gene Editing
  • Gene Knock-In Techniques / methods*
  • Human Embryonic Stem Cells / cytology
  • Humans
  • Leishmania donovani / genetics
  • Luminescent Proteins / genetics*
  • Recombinational DNA Repair / genetics
  • Transcription Activator-Like Effectors / metabolism*
  • Zinc Finger Nucleases / metabolism*

Substances

  • Luminescent Proteins
  • Transcription Activator-Like Effectors
  • DNA
  • Zinc Finger Nucleases