Figure 1

More than 4 shRNAs are needed to obtain 4 matched to all variants. Models predict that a minimum of 4 shRNAs is needed to prevent the emergence of viral escape mutants, however, this requires 4 shRNAs to be matched to all viral variants spanning the different subtypes. Unless all 4 shRNAs are 100% conserved across all targeted strains (unlikely) (A), then more than 4 shRNAs will be required to attain at least 4 matched to each different strain (B). By studying the intersecting conservations of combinations as a whole, combinations can be assembled such at at least 4 shRNAs (4+) for a given combination (of > 4 shRNAs) are matched to all relevant strains.