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-derived PAMs; (ii) provide a list of available Cas enzymes recognizing the SNV (s); (iii) propose mutational Cas-engineering to enhance the selectivity towards the SNV-derived PAM. With its ability to identify allele-specific genetic variants that can be targeted using already available or engineered Cas enzymes, AlPaCas is at the forefront of advancements in genome editing. AlPaCas is open to all users without a login requirement and is freely available at https://schubert.bio.uniroma1.it/alpacas.

AlPaCas: allele-specific CRISPR gene editing through a protospacer-adjacent-motif (PAM) approach / Rosignoli, Serena; Lustrino, Elisa; Conci, Alessio; Fabrizi, Alessandra; Rinaldo, Serena; Latella, Mariacarmela; Enzo, Elena; Prosseda, Gianni; DE ROSA, Laura; De Luca, Michele; Paiardini, Alessandro. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - 52:W1(2024), pp. W29-W38. [10.1093/nar/gkae419]

AlPaCas: allele-specific CRISPR gene editing through a protospacer-adjacent-motif (PAM) approach

Rosignoli Serena;Lustrino Elisa;Rinaldo Serena;Enzo Elena;Prosseda Gianni;De Rosa Laura;Paiardini Alessandro
2024

Abstract

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-derived PAMs; (ii) provide a list of available Cas enzymes recognizing the SNV (s); (iii) propose mutational Cas-engineering to enhance the selectivity towards the SNV-derived PAM. With its ability to identify allele-specific genetic variants that can be targeted using already available or engineered Cas enzymes, AlPaCas is at the forefront of advancements in genome editing. AlPaCas is open to all users without a login requirement and is freely available at https://schubert.bio.uniroma1.it/alpacas.
2024
gene; editing; gene therapy; crispr/cas; SNV
01 Pubblicazione su rivista::01a Articolo in rivista
AlPaCas: allele-specific CRISPR gene editing through a protospacer-adjacent-motif (PAM) approach / Rosignoli, Serena; Lustrino, Elisa; Conci, Alessio; Fabrizi, Alessandra; Rinaldo, Serena; Latella, Mariacarmela; Enzo, Elena; Prosseda, Gianni; DE ROSA, Laura; De Luca, Michele; Paiardini, Alessandro. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - 52:W1(2024), pp. W29-W38. [10.1093/nar/gkae419]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1711262
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