IN VIVO RNAi SCREEN FOR THE IDENTIFICATION OF HOST FACTORS RESTRICTING VIRAL REPLICATION

This technology allows the identification of host restriction factors that limit viral replication in a relevant animal model.

Standard siRNA screens are most often conducted in vitro using transformed cell lines and are therefore inherently non-physiological. However, by enabling siRNA delivery through replication-competent RNA viruses, natural selection can be harnessed to identify specific siRNAs that target proteins which limit viral replication.

The in vivo screen permits bona fide virus replication as the output, rather than requiring any subsequent manipulation (e.g., flow cytometry, western blotting, PCR) or relying on reporters, providing a more relevant and durable platform for identifying host factors.

Current Development Status

• Proof of concept enabled utilizing Sindbis virus and corroborated in several other RNA viruses

Applications

• Identification of targets for the generation of broad spectrum antivirals
• Identification of host factors that restrict:
• Viral replication
• Tropism
• Transmission
• Persistence

Advantages

• In vivo screening (reduction of screening artifacts)
• Robustness of the screen – this screen takes advantage of multiple fundamental biological principles: RNAi, natural selection, and viral pathogenesis

Publications

• Varble A et al. An in vivo RNAi screening approach to identify host determinants of virus replication. Cell Host and Microbe 2013. Sept 11;14(3):346-56
• Langlois R et al. In vivo delivery of cytoplasmic RNA virus-derived miRNAs. Molecular Ther. 2012 Feb;20(2):367-75
• Varble et al. Engineered RNA viral synthesis of microRNAs. Proc Natl Acad Sci USA 2010 Jun 22; 107(25):11519-24

Patent Status

• Patent applications pending in US, Canada, Europe, Japan, China (claiming priority from provisional serial 61/351,908, filed June 6, 2010)

Contact

Idoia Gamez, PhD, MBA
Business Development Director
Mount Sinai Innovation Partners | Icahn School of Medicine at Mount Sinai
Phone: 646.605.7317