Gene-edited cell models to study chronic wasting disease

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DOI

https://doi.org/10.3390/v14030609

Language of the publication
English
Date
2022-03-15
Type
Article
Author(s)
  • Thapa, Simrika
  • Marrero Winkens, Cristobal
  • Tahir, Waqas
  • Arifin, Maria I.
  • Gilch, Sabine
  • Schatzl, Hermann M.
Publisher
MDPI

Abstract

Prion diseases are fatal infectious neurodegenerative disorders affecting both humans and animals. They are caused by the misfolded isoform of the cellular prion protein (PrPC), PrPSc, and currently no options exist to prevent or cure prion diseases. Chronic wasting disease (CWD) in deer, elk and other cervids is considered the most contagious prion disease, with extensive shedding of infectivity into the environment. Cell culture models provide a versatile platform for convenient quantification of prions, for studying the molecular and cellular biology of prions, and for performing high-throughput screening of potential therapeutic compounds. Unfortunately, only a very limited number of cell lines are available that facilitate robust and persistent propagation of CWD prions. Gene-editing using programmable nucleases (e.g., CRISPR-Cas9 (CC9)) has proven to be a valuable tool for high precision site-specific gene modification, including gene deletion, insertion, and replacement. CC9-based gene editing was used recently for replacing the PrP gene in mouse and cell culture models, as efficient prion propagation usually requires matching sequence homology between infecting prions and prion protein in the recipient host. As expected, such gene-editing proved to be useful for developing CWD models. Several transgenic mouse models were available that propagate CWD prions effectively, however, mostly fail to reproduce CWD pathogenesis as found in the cervid host, including CWD prion shedding. This is different for the few currently available knock-in mouse models that seem to do so. In this review, we discuss the available in vitro and in vivo models of CWD, and the impact of gene-editing strategies.

Subject

  • Animal diseases,
  • Diseases

Keywords

  • Prion disease,
  • Bovine spongiform encephalopathies

Rights

Peer review

Yes

Identifiers

ISSN
1999-4915

Article

Journal title
Viruses
Journal volume
14
Journal issue
3
Article number
609
Accepted date
2022-03-11
Submitted date
2022-02-08

Citation(s)

Thapa, S., Marrero Winkens, C., Tahir, W., Arifin, M. I., Gilch, S., & Schatzl, H. M. (2022). Gene-edited cell models to study chronic wasting disease. Viruses, 14(3), 609. https://doi.org/10.3390/v14030609

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Animals

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