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Daniel Offen
Tel Aviv University
Corresponding Author
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Background CRISPR is a promising novel technology for treating genetic conditions. Therefore, it is essential to further develop and promote treatment’s safety and specificity. While the guide-RNA offers position-specific DNA targeting, it may tolerate small changes such as single-nucleotide polymorphisms (SNPs). To that end, an allele-specific targeting approach is in need for future treatments of heterozygous patients, suffering from genetic conditions caused by a SNP. The SNP-derived PAM approach allows highly allele-specific DNA cleavage by incorporating a protospacer adjacent motif (PAM) sequence only at the target allele. Description Here we present CrisPam, a tool that detects SNP-derived PAMs for allele-specific targeting by the CRISPR/Cas system. The algorithm scans the generation of each reported PAM for a given DNA sequence and its variations. A successful result is such that at least one PAM is generated by a SNP. Thus, the PAM shall be part of the variant allele only and the Cas protein will therefore be able to exclusively bind the variant allele for gene-editing, while the wildtype allele remains unchanged. Conclusion CrisPam is available online for researchers and also offers access to the CrisPamDB, a database that contains the CrisPam analysis for any reported pathogenic SNP in humans.
Keywords
CrisPam, Allele-specific, SNP-derived PAM, CRISPR tool, pathogenic SNP, SNP targeting, SNP-specific
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This is a preprint. It has not completed peer review.
Software
Daniel Offen
Tel Aviv University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 30 Apr, 2019
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Molecular Biology & Genetics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background CRISPR is a promising novel technology for treating genetic conditions. Therefore, it is essential to further develop and promote treatment’s safety and specificity. While the guide-RNA offers position-specific DNA targeting, it may tolerate small changes such as single-nucleotide polymorphisms (SNPs). To that end, an allele-specific targeting approach is in need for future treatments of heterozygous patients, suffering from genetic conditions caused by a SNP. The SNP-derived PAM approach allows highly allele-specific DNA cleavage by incorporating a protospacer adjacent motif (PAM) sequence only at the target allele. Description Here we present CrisPam, a tool that detects SNP-derived PAMs for allele-specific targeting by the CRISPR/Cas system. The algorithm scans the generation of each reported PAM for a given DNA sequence and its variations. A successful result is such that at least one PAM is generated by a SNP. Thus, the PAM shall be part of the variant allele only and the Cas protein will therefore be able to exclusively bind the variant allele for gene-editing, while the wildtype allele remains unchanged. Conclusion CrisPam is available online for researchers and also offers access to the CrisPamDB, a database that contains the CrisPam analysis for any reported pathogenic SNP in humans.
Figure 1
Figure 2
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