CRISPR/Cas9-based Targeted Genome Editing for the Development of Monogenic Diseases Models with Human Pluripotent Stem Cells

Curr Protoc Stem Cell Biol. 2018 May;45(1):e50. doi: 10.1002/cpsc.50. Epub 2018 Apr 26.

Abstract

Human pluripotent stem cells (hPSCs) represent a formidable tool for disease modeling, drug discovery, and regenerative medicine using human cells and tissues in vitro. Evolving techniques of targeted genome editing, specifically the CRISPR/Cas9 system, allow for the generation of cell lines bearing gene-specific knock-outs, knock-in reporters, and precise mutations. However, there are increasing concerns related to the transfection efficiency, cell viability, and maintenance of pluripotency provided by genome-editing techniques. The procedure presented here employs transient antibiotic selection that overcomes reduced transfection efficiency, avoids cytotoxic flow sorting for increased viability, and generates multiple genome-edited pluripotent hPSC lines expanded from a single parent cell. Avoidance of xenogeneic contamination from feeder cells and reduced operator workload, owing to single-cell passaging rather than clump passaging, are additional benefits. The outlined methods may enable researchers with limited means and technical experience to create human stem cell lines containing desired gene-specific mutations. © 2018 by John Wiley & Sons, Inc.

Keywords: CRISPR/Cas9; Stem cell; disease modeling; genome editing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Base Sequence
  • CRISPR-Associated Protein 9 / metabolism*
  • CRISPR-Cas Systems / genetics*
  • Cell Culture Techniques
  • Cell Proliferation
  • DNA / genetics
  • Freezing
  • Gene Editing / methods*
  • Genome, Human*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Models, Biological*
  • Plasmids / metabolism
  • Pluripotent Stem Cells / cytology*
  • RNA Splicing / genetics
  • RNA, Guide, CRISPR-Cas Systems / metabolism

Substances

  • Anti-Bacterial Agents
  • RNA, Guide, CRISPR-Cas Systems
  • DNA
  • CRISPR-Associated Protein 9