Liver Cancer Gene Discovery Using Gene Targeting, Sleeping Beauty, and CRISPR/Cas9

Julia E. Kieckhaefer; Flavio Maina; Rebecca G. Wells; Kirk J. Wangensteen

doi:10.1055/s-0039-1678725

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2019; 39(02): 261-274
DOI: 10.1055/s-0039-1678725

Review Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Liver Cancer Gene Discovery Using Gene Targeting, Sleeping Beauty, and CRISPR/Cas9

Authors

Julia E. Kieckhaefer

¹Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Flavio Maina

²Aix Marseille Univ, CNRS, Developmental Biology Institute of Marseille (IBDM) UMR 7288, Parc Scientifique de Luminy, Marseille, France
Rebecca G. Wells

¹Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

³Penn NCI Physical Sciences in Oncology Center PSOC@Penn and the NSF Center for Engineering MechanoBiology, University of Pennsylvania, Philadelphia, Pennsylvania
Kirk J. Wangensteen

¹Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Abstract

Hepatocellular carcinoma (HCC) is a devastating and prevalent cancer with limited treatment options. Technological advances have enabled genetic screens to be employed in HCC model systems to characterize genes regulating tumor initiation and growth. Relative to traditional methods for studying cancer biology, such as candidate gene approaches or expression analysis, genetic screens have several advantages: they are unbiased, with no a priori selection; can directly annotate gene function; and can uncover gene–gene interactions. In HCC, three main types of screens have been conducted and are reviewed here: (1) transposon-based mutagenesis screens, (2) knockdown screens using RNA interference (RNAi) or the CRISPR/Cas9 system, and (3) overexpression screens using CRISPR activation (CRISPRa) or cDNAs. These methods will be valuable in future genetic screens to delineate the mechanisms underlying drug resistance and to identify new treatments for HCC.

Keywords

hepatocellular carcinoma - genetic screening - Sleeping Beauty transposon - CRISPR - hydrodynamic injection

Full Text

References

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