biostudies-literatureRosignoli STelethonEuropean Research CouncilItaly Ministry of University and Research PRINAssociazione Italiana Ricerca sul CancroSapienza University of RomeW29-W38https://www.ebi.ac.uk/biostudies/studies/S-EPMC11223865biostudies-literatureUnknown52(W1)Gene therapy of dominantly inherited genetic diseases requires either the selective disruption of the mutant allele or the editing of the specific mutation. The CRISPR-Cas system holds great potential for the genetic correction of single nucleotide variants (SNVs), including dominant mutations. However, distinguishing between single-nucleotide variations in a pathogenic genomic context remains challenging. The presence of a PAM in the disease-causing allele can guide its precise targeting, preserving the functionality of the wild-type allele. The AlPaCas (Aligning Patients to Cas) webserver is an automated pipeline for sequence-based identification and structural analysis of SNV-derived PAMs that satisfy this demand. When provided with a gene/SNV input, AlPaCas can: (i) identify SNV-deriveNucleic acids researchAlPaCas: allele-specific CRISPR gene editing through a protospacer-adjacent-motif (PAM) approach.PMC11223865101019289GGP20088RM1221815D52AB322022N3JXLA20447Conci ALustrino EEnzo ELatella MCDe Luca MFabrizi ARinaldo SProsseda GDe Rosa LRosignoli SPaiardini AfalseAlPaCas: allele-specific CRISPR gene editing through a protospacer-adjacent-motif (PAM) approach.Gene therapy of dominantly inherited genetic diseases requires either the selective disruption of the mutant allele or the editing of the specific mutation. The CRISPR-Cas system holds great potential for the genetic correction of single nucleotide variants (SNVs), including dominant mutations. However, distinguishing between single-nucleotide variations in a pathogenic genomic context remains challenging. The presence of a PAM in the disease-causing allele can guide its precise targeting, preserving the functionality of the wild-type allele. The AlPaCas (Aligning Patients to Cas) webserver is an automated pipeline for sequence-based identification and structural analysis of SNV-derived PAMs that satisfy this demand. When provided with a gene/SNV input, AlPaCas can: (i) identify SNV-derive2024-01-01T00:00:00Z2024 Jul2026-06-02T22:49:29.348Z2025-04-04T12:22:06.565ZS-EPMC112238653879506810.1093/nar/gkae419