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SynDesign provides systematic gene targeting, automated saturation genome editing (SGE) with efficiency prediction using DeepPrime/DeepPrime-FT, and seamless integration of library construction for functional evaluation studies using precision pegRNA libraries.
Press the Load Example button to run SynDesign with the reference example, after configuring the desired Input Format.
Choose model conditions closest to experimental parameters.
Recommended: PE2max with optimized scaffold in HEK293T cells
Select the type of edit (substitution, insertion, deletion) and the length of the edit, if the option is available.
Select the minimum and maximum PBS lengths to consider. Default: 7-15.
Select the maximum length of the RTT (up to 40 bp). Default: 40.
Choose the priority for silent markers between the left homology arm (LHA), a PAM edit and the right homology arm (RHA): Default, LHA only, PAM edit only, or RHA only.
Schematic of selected region(s) for inducing synonymous mutation markers:
A target near an exon boundary puts part of this window outside the coding sequence. Intronic bases belong to no codon, so there is no synonymous change to make in them and a marker can only be placed in the coding part:
The pegRNA itself is unaffected — it is designed from the coordinates either way. It is the synonymous marker, and only the marker, that needs a reading frame.
Select the number of top guides to display in results. Default: 200.
SynDesign supports multiple input formats:
FASTA: Upload or enter FASTA sequence(s) to perform SGE on the provided sequence(s). The recommended sequence length is >= 121 bp, where a 60 bp flank on either side of the target site gives the fullest set of pegRNA designs; a shorter sequence is designed from and offers fewer.
GeneSym: Gene Symbol (e.g., BRCA1) and Exon Number.
NMID: RefSeq NM ID and Exon Number.
Ensembl: Ensembl Gene ID and Exon Number.
HGNC: HGNC ID and Exon Number.
ClinVar: ClinVar ID and Analysis Mode (Model/Correction). Use the numeric Variation ID (e.g., 9325), the VCV accession (e.g., VCV000009325.76), a ClinVar record (RCV) or submission (SCV) accession, or a dbSNP rs number (e.g., rs80357382). An RCV or SCV accession names an interpretation or a submission rather than the variant, and its digits are not the Variation ID, so it is looked up in the bundled ClinVar release and translated to the Variation ID behind it, with the translation stated in the job log; one the bundled release does not carry is refused, with the reason.
9325
VCV000009325.76
rs80357382
COSMIC: COSMIC ID and Analysis Mode (Model/Correction).
Sequence: Custom Unedited and Edited Sequences. The edit is read from the difference between the pair, wherever it sits in them. A 121 bp sequence — 60 bp of flank on each side of the edit — offers the fullest set of pegRNAs, because it is the shortest input in which every candidate's scoring window fits; a shorter pair is designed from and offers fewer candidates. No pair is skipped for its length.
Position: Genomic Position for GRCh38 (chr & coordinates).
When uploading files, press the [+] button to add files. Uploaded files can be cleared by pressing either of the checkmark buttons.
Inputs that specify an edit. An unedited/edited sequence pair, ClinVar ID and COSMIC ID name the edit to install, and the pegRNA is designed to write it. No separate homology-directed repair (HDR) donor is offered on this workflow: in prime editing the pegRNA's own reverse-transcription template is the repair template, so a second single-stranded donor would be a different experiment rather than an extra column.
A list of available gene symbols and annotation IDs can be found in this Text File.
Note: GeneSym, NMID, Ensembl, HGNC, and Position inputs may take dozens of minutes to hours for large inputs. Long sequences in FASTA mode will also similarly increase processing time.
