Gene-Edited Cell Models to Study Chronic Wasting Disease.

Area of Science:

• Neurodegenerative Diseases
• Prion Biology
• Animal Health

Background:

• Prion diseases, including Chronic Wasting Disease (CWD), are fatal neurodegenerative disorders caused by misfolded prion proteins.
• CWD is highly contagious in cervids, with significant environmental shedding, necessitating better research models.
• Current cell culture and animal models have limitations in robustly propagating CWD prions and fully recapitulating disease pathogenesis.

Purpose of the Study:

• To review and discuss available in vitro and in vivo models for studying Chronic Wasting Disease (CWD).
• To highlight the impact of gene-editing strategies, such as CRISPR-Cas9, on developing improved CWD models.
• To assess the utility of these models for prion quantification, biological studies, and therapeutic screening.

Main Methods:

• Review of existing literature on CWD cell culture and animal models.
• Analysis of gene-editing techniques, specifically CRISPR-Cas9, applied to prion protein (PrP) gene modification.
• Comparison of different model systems, including transgenic and knock-in mice, for CWD prion propagation and pathogenesis.

Main Results:

• Gene-editing has enabled the development of cell and animal models with enhanced CWD prion propagation.
• Knock-in mouse models show promise in reproducing CWD pathogenesis and prion shedding observed in cervids.
• Limited cell lines currently support robust CWD prion propagation, underscoring the need for improved in vitro systems.

Conclusions:

• Gene-editing technologies are pivotal in advancing the creation of more accurate and effective CWD research models.
• Improved in vitro and in vivo models are essential for understanding CWD's molecular mechanisms and for developing therapeutic interventions.
• Further development of models that mimic cervid CWD pathogenesis, including prion shedding, is critical for disease control.