Paralog off-target rule

Scope. Applies to all nucleic-acid-targeting modalities: CRISPR (h07), ASO (h08), prime editing (h07), siRNA.

Rule. Every guide/pegRNA/oligo must be:

  1. Tested in-silico against STRCP1 (BLAST-N, pairwise, Cas-OFFinder on STRCP1 sequence)
  2. Require ≥3-mismatch discrimination or PAM-breaking polymorphism
  3. Wet-lab validated on STRCP1-expressing controls before in-vivo

Known tractable windows. STRC Pseudogene Problem documents regions of STRC with enough paralog divergence for discriminating design.

Violators flagged at review. A phase proof cannot claim green status without the paralog discrimination table.

Connections