SNP-CRISPR: A Web Tool for SNP-Specific Genome Editing

Chen, Chiao-Lin; Rodiger, Jonathan; Chung, Verena; Viswanatha, Raghuvir; Mohr, Stephanie E.; Hu, Yanhui; Perrimon, Norbert

doi:10.1534/g3.119.400904

Cited by 42 publications

(24 citation statements)

References 39 publications

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“…Furthermore, both studies emphasize the need of common gRNA designs due to regulations and its consequential costs. Another recently published web tool, SNP-CRISPR, designs gRNAs for non-reference genomes to support allelic targeting (Chen et al, 2020). SNP-CRISPR calculates the gRNA efficiency score for the variant and the reference sequences.…”

Section: Snp-derived Pammentioning

confidence: 99%

CrisPam: SNP-Derived PAM Analysis Tool for Allele-Specific Targeting of Genetic Variants Using CRISPR-Cas Systems

et al. 2020

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Clustered regularly interspaced short palindromic repeats (CRISPR) is a promising novel technology that holds the potential of treating genetic diseases. Safety and specificity of the treatment are to be further studied and developed prior to implementation of the technology into the clinic. The guide-RNA (gRNA) allows precise position-specific DNA targeting, although it may tolerate small changes such as point mutations. The permissive nature of the CRISPR-Cas system makes allele-specific targeting a challenging goal. Hence, an allele-specific targeting approach is in need for future treatments of heterozygous patients suffering from diseases caused by dominant negative mutations. The single-nucleotide polymorphism (SNP)-derived protospacer adjacent motif (PAM) approach allows highly allele-specific DNA cleavage due to the existence of a novel PAM sequence only at the target allele. Here, we present CrisPam, a computational tool that detects PAMs within the variant allele for allele-specific targeting by CRISPR-Cas systems. The algorithm scans the sequences and attempts to identify the generation of multiple PAMs for a given reference sequence and its variations. A successful result is such that at least a single PAM is generated by the variation nucleotide. Since the PAM is present within the variant allele only, the Cas enzyme will bind the variant allele exclusively. Analyzing a dataset of human pathogenic point mutations revealed that 90% of the analyzed mutations generated at least a single PAM. Thus, the SNP-derived PAM approach is ideal for targeting most of the point mutations in an allele-specific manner. CrisPam simplifies the gRNAs design process to specifically target the allele of interest and scans a wide range of 26 unique PAMs derived from 23 Cas enzymes.

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Section: Snp-derived Pammentioning

confidence: 99%

CrisPam: SNP-Derived PAM Analysis Tool for Allele-Specific Targeting of Genetic Variants Using CRISPR-Cas Systems

et al. 2020

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“…Basically, SNP-CRISPR designs sgRNAs based on the public SNP database yet with only two types of PAM. 53 The other server, CrisPam, only analyzes the variants that produce novel PAMs (in PAM) from pathogenic and likely pathogenic SNPs in humans. 54 Interestingly, they found that 84% of the total SNPs checked can create novel PAMs, and the average number of PAMs generated by an SNP is 6.97.…”

Section: Comparison With Similar Serversmentioning

confidence: 99%

AsCRISPR: A Web Server for Allele-Specific Single Guide RNA Design in Precision Medicine

Zhao

Tang

2020

The CRISPR Journal

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“…Another two web servers, SNP-CRISPR and CrisPam, were also recently developed, converging with our web tool, AsCRISPR, but at different publication status, to share the same notion of the allele-specific designing of sgRNAs. Basically, SNP-CRISPR designed the sgRNAs based on public SNP database yet with only two types of PAMs [41]. Another web server, CrisPam, only analyzed the variants that produce novel PAMs (In PAM) from pathogenic and likely-pathogenic SNPs in humans [42].…”

Section: Comparison With Similar Serversmentioning

confidence: 99%

AsCRISPR: a web server for allele-specific sgRNA design in precision medicine

Zhao

Tang

2019

Preprint

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Allele-specific targeting by CRISPR provides a point of entry for personalized gene therapy of dominantly inherited diseases, by selectively disrupting the mutant alleles or diseasecausing single nucleotide polymorphisms (SNPs), ideally while leaving normal alleles intact. Despite unprecedented specificity and tremendous therapeutic utility of allelespecific targeting by CRISPR, few bioinformatic tools have been implemented for the allele-specific purpose. We thus developed AsCRISPR (Allele-specific CRISPR), a web tool to aid the design of guide sequences that can discriminate between alleles. It can process with query sequences harboring single-base or short insertion-deletion (indel) mutations, as well as heterozygous SNPs deposited in the dbSNP database. Multiple CRISPR nucleases and their engineered variants including newly-developed Cas12b and CasX are included for users' choice. AsCRISPR provides the downloadable results of candidate guide sequences that may selectively target either allele. Meanwhile, AsCRISPR evaluates the on-target efficiencies, specificities and potential off-targets of those candidates, and also displays the restriction enzyme sites that might be disrupted upon successful genome edits. Other than designing allele-specific guide sequences for treating diseases, AsCRISPR could also be exploited to help studying the potential functions of genetic variants at certain gene loci by applying allele-specific editings. AsCRISPR is freely available at http://www.genemed.tech/ascrispr.

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SNP-CRISPR: A Web Tool for SNP-Specific Genome Editing

Cited by 42 publications

References 39 publications

CrisPam: SNP-Derived PAM Analysis Tool for Allele-Specific Targeting of Genetic Variants Using CRISPR-Cas Systems

CrisPam: SNP-Derived PAM Analysis Tool for Allele-Specific Targeting of Genetic Variants Using CRISPR-Cas Systems

AsCRISPR: A Web Server for Allele-Specific Single Guide RNA Design in Precision Medicine

AsCRISPR: a web server for allele-specific sgRNA design in precision medicine

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