CRISPR-Based Pooled Screening for Host Factors Modulating HCV Antiviral Resistance Evolution

While much research (e.g., El-Sokkary et al., 2020) focuses on viral mutations conferring resistance, the role of host genetics in shaping resistance evolution is underexplored. This idea proposes large-scale CRISPR screens in hepatocyte models infected with HCV and subjected to DAAs. By identifying host factors whose loss or gain accelerates or retards resistance emergence, this study could uncover novel druggable pathways or resistance “gatekeepers.” This approach is distinct from purely viral-centric resistance studies and could explain some of the conflicting clinical observations around resistance rates (Tavares et al., 2018). It fits squarely within the “explore novel techniques” heuristic and could revolutionize both our understanding of resistance and the development of host-targeted therapies.

References:

1. Molecular Characterization of Hepatitis C Virus for Developed Antiviral Agents Resistance Mutations and New Insights into in-silico Prediction Studies. M. A. El-Sokkary, Lizaveta Gotina, M. M. Al-Sanea, A. Pae, R. Elbargisy (2020). Infection and Drug Resistance.
2. Prevalence of resistance-associated substitutions to direct-acting antiviral agents in hemodialysis and renal transplant patients infected with hepatitis C virus. Rita Tavares, A. Feldner, J. Pinho, F. Malta, R. Carvalho-Filho, R. Santana, Vanessa Fusco Duarte de Castro, G. Dastoli, Juliana Custódio Lima, M. L. Ferraz (2018). Infection and Drug Resistance.