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

Autor:	Rosignoli S; Department of Biochemical Sciences 'A. Rossi Fanelli', Sapienza University of Rome, Rome 00185, Italy., Lustrino E; Department of Biochemical Sciences 'A. Rossi Fanelli', Sapienza University of Rome, Rome 00185, Italy., Conci A; Centre for Regenerative Medicine 'Stefano Ferrari', Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy., Fabrizi A; Centre for Regenerative Medicine 'Stefano Ferrari', Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy., Rinaldo S; Department of Biochemical Sciences 'A. Rossi Fanelli', Sapienza University of Rome, Rome 00185, Italy., Latella MC; Holostem s.r.l, Via Gottardi 100, 41125 Modena, Italy., Enzo E; Centre for Regenerative Medicine 'Stefano Ferrari', Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy., Prosseda G; Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome 00185, Italy., De Rosa L; Centre for Regenerative Medicine 'Stefano Ferrari', Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy., De Luca M; Centre for Regenerative Medicine 'Stefano Ferrari', Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy., Paiardini A; Department of Biochemical Sciences 'A. Rossi Fanelli', Sapienza University of Rome, Rome 00185, Italy.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Jul 05; Vol. 52 (W1), pp. W29-W38.
DOI:	10.1093/nar/gkae419
Abstrakt:	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. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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