From grimoire
Designs CRISPR-Cas9/Cas12/Cas13 gene editing experiments: selects guide RNAs, evaluates on-target efficiency and off-target risk, chooses delivery strategy, and designs editing confirmation assays.
How this skill is triggered — by the user, by Claude, or both
Slash command
/grimoire:apply-crispr-design-principlesThe summary Claude sees in its skill listing — used to decide when to auto-load this skill
Design a CRISPR genome editing experiment by selecting high-efficiency guide RNAs with minimal off-target potential, choosing appropriate delivery and selection strategies, and building in rigorous editing confirmation assays.
Design a CRISPR genome editing experiment by selecting high-efficiency guide RNAs with minimal off-target potential, choosing appropriate delivery and selection strategies, and building in rigorous editing confirmation assays.
Adopted by: NIH, Broad Institute, Wellcome Sanger Institute, and every major research institution conducting genome editing use systematic CRISPR design tools (Benchling, CRISPOR, CHOPCHOP, Cas-OFFinder) rather than ad hoc guide selection. The FDA's guidance on CRISPR-based therapeutics requires comprehensive off-target analysis as a prerequisite for IND filing. Impact: Doench et al. (2016) showed that guide RNA efficiency varies by more than 100-fold depending on sequence context — random guide selection produces high failure rates. Hsu et al. (2013) demonstrated that off-target cleavage occurs at sequences with up to 5 mismatches, particularly in the seed region — making systematic off-target prediction essential. The first human CRISPR clinical trials (Vertex/CRISPR Therapeutics CTX001) validated that systematic design followed by rigorous confirmation produces safe editing outcomes.
Before designing any guide RNA:
The goal determines which Cas variant (Cas9, Cas12a, base editors, prime editors) is appropriate.
Rules for standard Cas9 (SpCas9, requires NGG PAM):
Off-target cleavage is the primary safety concern:
Match delivery to cell type and context:
Confirming successful editing is mandatory:
For most applications: sort or limit-dilute after transfection to obtain clonal populations; sequence both alleles to confirm bi-allelic editing.
npx claudepluginhub jeffreytse/grimoire --plugin grimoireProvides three-tiered sgRNA design guide for CRISPR experiments using validated Addgene sequences, CRISPick pre-computed datasets, or de novo rules.
Designs PCR experiments with primer design, thermal cycling optimization, control selection, and troubleshooting for reliable DNA/RNA amplification.
Router that dispatches bioinformatics and statistical analysis tasks to specialized skills for RNA-seq, variant calling, phylogenetics, single-cell, proteomics, and more.