Fast. Comprehensive. Expert-led.
Unlock the full potential of CRISPR screens in human iPSC-derived cells in an instant with our expert service, optimised workflows and unparalleled results.
Flexible
Comprehensive suite of fully customisable and scalable service options supported by a broad range of functional readout capabilities.
Confident
Expert-led path from concept to results for accurate and reproducible actionable insights.
Cost-effective
Fast results without the need to establish and validate CRISPR-based functional genomic screening in-house so you can focus on results.
CRISPR modalities
Our services support all common CRISPR modalities (CRISPRko, CRISPRi, and CRISPRa) and enable large-scale studies across diverse biological processes and disease areas.
CRISPRko Knockout
Frameshift mutations caused by Cas9-mediated double-strand breaks and subsequent NHEJ (non-homologous end-joining) resulting in complete loss-of-function.
CRISPRi Interference
Dead (d) Cas9 is fused with a transcriptional repressor that modulates gene expression. The guide RNA directs dCas9 to a target site, where it blocks transcription without altering the DNA sequence.
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CRISPRa Activation
dCas9 is fused to a transcriptional activator, which is directed to a target site by the guide RNA. The binding will result in an activation, increasing the expression of the target gene.
Our service packages
Across all service options, our experts will partner with you to design and deliver CRISPR-based functional genomic screens tailored to your research goals. At the start of each project, we will define requirements, deliverables and timelines, and keep you in the loop with regular update meetings throughout.
*All our service options are fully customisable. If you require alternative human iPSC-derived cells, bespoke protocols or workflows, or wish to adapt any of our portfolio cell types or disease models that are not CRISPR-ready, simply let us know and we will work with you to accommodate your requirements.
Our services
Our services
CRISPR-Screening in 3 easy steps – our approach
| Step 1 - Project design |
Choose your CRISPR-Ready ioCell type We offer a wide range of CRISPR-Ready ioCells for your research projects. We currently support CRISPR knockout, activation, and inhibition screens, as well as CRISPRko-Ready ioDisease Model Cells. All our CRISPR Ready cells are highly characterised and undergo a comprehensive series of quality checks to ensure highly accurate, scalable and reproducible results. Should your project however require different cell types or disease model cells, we can work with you to develop the appropriate model system customised to your specific research needs. |
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Select the genes of interest Whether targeted pathways or genome wide screens, our experts will design a bespoke sgRNA library using our proprietary guide RNA design algorithm and cloning pipeline based on your selected genes. |
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Specify the CRISPR modality Select the CRISPR modality required for your research goals: CRISPRko (knockout), CRISPRi (interference), and CRISPRa (activation). |
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Define additional functional readouts (if required) Choose from a range of functional readouts including high-throughput viability assays, fluorescence-based phenotypic screens, and next-generation sequencing (NGS) approaches. |
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| Step 2 - CRISPR screen |
Leave your CRISPR screens in expert hands Our experts will carry out pooled scCRISPR screens based on perturb seq/CROP seq methodologies for you, ensuring every step of the workflow is meticulously optimised. Every single cell in the pool will carry a different perturbation for a different gene. |
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Single-cell library preparation Each cell is isolated in a microscopic droplet alongside a uniquely barcoded bead. As the cell's RNA is processed on the bead, it generates a distinct "transcriptomic fingerprint," allowing us to precisely map the effects of each CRISPR perturbation cell by cell. |
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Guide capturing and mapping By mapping the guide RNAs, we can link each cell's unique transcriptomic fingerprint directly to the exact CRISPR perturbation that caused it. |
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| Step 3 - Data analysis and transfer |
Access your results We provide a comprehensive analysis of high-content datasets containing single-cell transcriptomic profiling for each genetic perturbation, together with additional functional readout data where selected. If you need additional help with data analysis or interpretation, our dedicated team of in-house bioinformaticians will be available to support you further. |
*All our service options are fully customisable. If you require alternative human iPSC-derived cells, bespoke protocols or workflows, or wish to adapt any of our portfolio cell types or disease models that are not CRISPR-ready, simply let us know and we will work with you to accommodate your requirements.
Applying human cells in CRISPR screens
This webinar explores how CRISPR-Cas9 is a vital tool for functional genomics, aiding in identifying genomic variations linked to diseases and validating drug targets. The experts also discuss scalable tools for gene characterisation and advances in leveraging human iPSC-derived cell technologies for CRISPR-based knockouts.
Actionable insights revealed by CRISPR-based functional genomics screening
A pooled single-cell CRISPR knockout screen uncovers modulators of microglia activation.
Figure 1: Log2FC profiles for gene knockouts with a cosine similarity >0.3 compared to cells with non-targeting guides in the unstimulated condition
Experimental Setup: We selected 110 candidate genes for a pooled scCRISPR screen based on their known roles in neurodegeneration and neuroinflammation. Guide RNAs were delivered via lentiviral transduction on day 10, aiming for a single integration per cell. The cells were cultured and then treated with +/- LPS for 24 hours before single cell processing on day 15. Cosine similarity analysis compared knockouts in LPS-treated CRISPR-Ready ioMicroglia to both resting and activated states.
Results: The analysis identified 17 gene knockouts with an altered response to LPS stimulation including CD14, MAP3K7, TIRAP, IKBKG, TRAF6, IKBKB, LY96, TICAM1, RELA, and TLR4 known to be involved in LPS activation mediated via the TLR4 signalling pathway.
A pooled knockout screen of neurodegenerative disease-relevant genes in CRISPR-Ready ioGlutamatergic Neurons shows clustering of aaRS genes in UMAPs
For a pooled knockout screen in CRISPR-Ready ioGlutamatergic Neurons, 100 known genes involved in neurodegenerative diseases were selected. Lentiviral transduction of the gRNAs was carried out on day 3, and single-cell gene expression analysis was performed on day 12. Single cells were clustered on uniform manifold approximations and projections (UMAPs) based on their shared nearest neighbour’s gene expression. Clustering of aminoacyl-tRNA synthetase (aaRSs) knockouts including AARS1, HARS1, CARS1, and GARS1 was observed. In contrast, cells transduced with non-targeting control sgRNAs were evenly distributed among clusters. Pathway analysis showed gRNAs targeting aaRSs activated the unfolded protein response (UPR), the mechanism by which cells control endoplasmic reticulum protein homeostasis. In many neurodegenerative diseases, signs of UPR activation have been reported. The most common aaRS-associated monogenic disorder is the incurable neurodegenerative disease Charcot–Marie–Tooth neuropathy (CMT).
CRISPR-Ready ioCells development
Using CRISPR-Ready ioCells eliminates the need to spend months engineering and characterising Cas9-stable iPSC lines and optimising differentiation protocols, significantly reducing experimental timelines. With these ready-to-screen cells, reliable and reproducible experimental results can be achieved quickly.
If we do not currently have the cells your target identification and validation workflows need, our team of experts can develop new CRISPR-Ready ioCells in any ioWild Type Cell background.
Do you have your own human iPSC-derived cells?
We have got you covered - all our service options are designed to be fully customisable. We can integrate your established human iPSC-derived cell models and differentiation protocols, so you can leverage your resources while benefiting from our CRISPR screening expertise.
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