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Viruses exploit high-dimensional RNA structures to facilitate viral replication and impede host restriction. Here, a novel next-generation sequencing (NGS)-based screening workflow, called Fate-seq, was used to define and characterize high-dimensional RNA structures from the severe acute respiratory syndrome coronavirus (SARSCoV) genome in an unbiased, high-throughput, and comprehensive manner. The Fate-seq workflow leverages 300mer Twist Oligos to simplify library preparation and capture genomic sequences long enough to probe RNA secondary structures.