sgRNA Array Designer — Express Many Guides From One Non-Repetitive Cassette
Build a multiplexed CRISPR array that expresses up to 27 sgRNAs from one construct and shares no long stretch with itself — the property that stops it recombining away and getting refused by synthesis vendors.
Design a multiplexed CRISPR sgRNA array that expresses many guides from one cassette without repeating the same parts along it. A Cas9 sgRNA scaffold is about 61 bases of fixed sequence, so the obvious construction puts one identical copy of it per guide into a single molecule, together with identical promoters and terminators; that array recombines with itself in the cell, losing guides silently, and synthesis vendors delay or refuse it. This tool draws each transcription unit's promoter, scaffold variant and insulator from a measured, non-repetitive collection, selecting across all three part pools at once rather than within each type, because a promoter and a scaffold can each be clean within their own pool while sharing a long stretch with each other. It then re-measures the finished molecule, since a repeat spanning the end of one handle and the start of the next promoter exists in neither part. It takes guides and does not choose them.
Paste the protospacers you want to express together to build a non-repetitive array.
Design, edit, and verify complete constructsSeqStudio combines sequence editing and annotation, plasmid maps, primer/cloning/CRISPR design, Sanger verification, and GenBank/SnapGene files in one workspace.
How to use the sgRNA Array Designer tool
- 1Check the capacity line first: it states how many sgRNAs fit at each threshold, which is a property of the parts collection rather than of your guides.
- 2Paste your protospacers, one per line, 20 nt and without the PAM; the PAM is in the genome, not in the array.
- 3Pick a maximum shared length. Lower gives a more stable array built from fewer available parts; the scaffold pool offers 12 parts at 12 bp, 18 at 15 and 24 at 20.
- 4Read the per-unit table, where every unit must show a different promoter and handle, then download the annotated GenBank.
Frequently asked questions
Why not repeat the same scaffold twenty times?
The construct can be built, and it will often work at first. The twenty identical copies give homologous recombination twenty substrates, so the array loses guides in culture; because each remaining sgRNA is still expressed from an intact-looking cassette, the screen returns some targets repressed and some not, which reads as biology rather than as instability. The same repetition is what makes synthesis vendors delay or refuse the order.
Where do the scaffold variants come from, and can I trust them?
They were measured in cells rather than predicted: each scaffold variant was shown to work, not assumed to. The collection holds 27 scaffolds, which is the hard ceiling on array length; the published work itself demonstrated arrays of 22.
Why does a lower threshold give me fewer sgRNAs?
Because the pools are not mutually non-repetitive at every threshold; selecting from them is the point. At a maximum shared length of 20 bases, 24 of the 27 scaffolds can coexist; at 12 bases only 12 can; at 8 bases, three. You are choosing how much residual similarity to accept, and the whole curve is reported so the choice is visible rather than implied.
Does this pick my guides or tell me how well they will work?
No, deliberately. An array of twenty useless guides assembles perfectly, and nothing about the array's sequence says anything about knockdown. Use the gRNA designer and the off-target checker to choose guides; both carry their own accuracy statements, because guide activity is a modelled estimate while this assembly is a determinate consequence of its inputs.
What is the insulator for, and can I turn it off?
It is neutral DNA between transcription units, keeping one unit's terminator from interfering with the next unit's promoter. Turning it off removes the spacer pool from the selection, which occasionally lets a longer array fit at a low threshold; the trade is visible in the pool-usage line.
It found repeats in my array anyway. How?
Two ways, and the tool distinguishes them. Either two of your guides are identical or near-identical, which no choice of parts can fix, or a repeat was created by a junction, the end of one handle plus the start of the next promoter, and exists in neither part. That is why the assembled molecule is re-measured rather than only the parts.