CRISPR-cas technology as a tool to create animal models for biomedical research

Abhiraami Kannan Sundhari, Shalini Kamu Reddy, Katherina Walz, Channabasavaiah B. Gurumurthy, Rolen M. Quadros

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Early approaches to create gene-modified animal models involved chemical (e.g., N-ethyl-N-nitrosourea) and physical (e.g., radiation) mutagenesis methods; however, the precise location of the mutations in these models was not easy to discern. These forward genetics approaches generated many useful models for biomedical research. In the 1980s, technologies involving the injection of DNA cassettes into fertilized zygotes or the injection of gene-modified embryonic stem (ES) cells into blastocysts were developed. These technologies enabled the creation of transgenic animals or precise modification of known genes, leading to the birth of a new era of reverse genetics (genetic engineering). Mice have been used as the platform for these forward and reverse genetics technologies to develop during the past three decades. With the development of programmable nucleases such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), and the discovery of clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated (Cas9) gene editing tool, the genetic engineering technologies-particularly reverse genetic approaches-started to undergo radical change. Even though ZFNs and TALENs are still in use, the CRISPR-Cas9 system has been dominating the field. The CRISPR-Cas9 tool is now used in almost any species to generate specific genetic modifications. In this chapter we briefly describe the history of genetic engineering, introduce the latest programmable nucleases, and discuss in some detail the application of the CRISPR-Cas9 system as a genome editing tool for creating model organisms for biomedical research.

Original languageEnglish (US)
Title of host publicationCellular and Animal Models in Human Genomics Research
PublisherElsevier
Pages141-153
Number of pages13
ISBN (Electronic)9780128165737
DOIs
StatePublished - Jan 1 2019

Keywords

  • Animal models
  • CRISPR-Cas9
  • Embryonic stem cells
  • Genome editing
  • Knockout and transgenic

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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