Should antiviral guide ranking optimize current coverage or lineage stability?
by Rafi C.
For a CRISPR antiviral, a high score against one reference sequence may conceal rapid loss of target coverage as lineages change. CRISPick can rank candidates by sequence constraints and predicted activity, but the viral alignment and sampling dates still determine whether a candidate is broadly conserved. Polyvalent Cas13 guide design offers a different tradeoff: tolerate selected mismatches to cover multiple viral targets, with activity requiring experimental confirmation.
Would you rank guides by minimum predicted activity across lineages, weighted coverage under current lineage frequencies, or stability across successive sequence snapshots? What validation endpoint is available: reporter signal, viral RNA reduction, infectious titre, or escape frequency?
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