Vivlion GmbH

🎉 Celebrating a decade of CRISPR screening: Back to 2015 🎉 For 2015, we chose to highlight a landmark publication by first author Traver Hart and the team around Jason Moffat from University of Toronto (Hart et al., Cell 2015). The publication stands out as the first comprehensive CRISPR screening using multiple contexts to study general cell fitness and synthetic lethal interactions. It opened avenues for the development of targeted therapies that can exploit cancer vulnerabilities, offering more effective and personalized treatment options for patients.   Summary of key findings and impact: ▶ Comprehensive gene mapping: Using high-resolution, genome-wide CRISPR screens, the first set of core essential fitness genes were identified. These are crucial for the survival of cells, and, today, serve as critical controls for most unbiased screens. These genes also represent potential targets for novel therapies, as inhibiting them could impair cancer cell growth without affecting healthy cells. ▶ Personalized therapeutic targets: The study's high-resolution approach also revealed genotype-specific cancer liabilities, or genetic weaknesses unique to particular cancer mutations. These findings underscored the importance of tailoring cancer treatments to a patient's specific genetic makeup, advancing the field of personalized medicine. ▶ Advancing drug discovery: Demonstrating the efficacy of CRISPR-Cas9 in large-scale genetic screens, the study underscored the transformative potential of gene editing technologies in functional genomics and therapeutic discovery. The team uncovered new therapeutic targets, which could be exploited in the development of cancer therapies. This approach was particularly important for addressing cancers that were resistant to conventional treatments.   In 2015, this study was a game changer, demonstrating the potential of #CRISPRscreening as a tool for dissecting the complex genetic dependencies of cancer cells. It did not only enhance our understanding of cancer biology, but also marked a crucial step towards the realization of precision oncology, offering hope for more targeted, less toxic therapies for cancer patients.

🎉 Celebrating a decade of CRISPR screening: Back to 2014 🎉 To the best of our knowledge, the first genome-wide screens utilizing CRISPR/Cas9 in human cells were published back-to-back by Feng Zhang (Shalem et al., Science 2014) and by Eric Lander and David Sabatini (Wang et al., Science 2014). The team around Zhang developed a genome-scale CRISPR-Cas9 knockout (GeCKO) library for lentiviral delivery and targeting over 18,000 human genes with 64,000 unique guide sequences. They showed that this innovative approach enables both negative and positive selection screening in human cells and demonstrated that CRISPR screening could overcome some of the limitations of RNAi, such as off-target effects and incomplete knockdown. The team successfully identified essential genes for cell viability in cancer and stem cells and uncovered genes linked to drug resistance in melanoma. They utilized their CRISPR screening data to infer genetic networks that underlie drug resistance mechanisms, providing a broader understanding of cellular response to treatment. Lander’s and Sabatini’s teams used a library with 73,000 gRNAs in a range of pooled screening approaches. They systematically identified and cataloged essential genes, which are fundamental to cell survival, identified novel tumor suppressors and new biological roles of known proteins in drug resistance, establishing CRISPR screening as a suitable tool for insights into gene function and drug resistance mechanisms. They also showed that certain sequence characteristics of sgRNAs can influence their effectiveness. These two publications mark a significant milestone in genetic research, setting the stage for widespread adoption of CRISPR/Cas9 as a standard technique for high-throughput functional genomics in the pre-clinical value chain. 🥂🚀

🎉 Celebrating a decade of CRISPR screening! 🎉 Can you believe it's been a good ten years since CRISPR screening first revolutionized preclinical research? Since then, we've seen breakthroughs in understanding gene functions, uncovering disease mechanisms and identifying novel therapeutic targets - all thanks to this incredible high-throughput gene editing technology. The Vivlion team is proud to be part of this revolution and accelerate target discovery and pre-clinical drug development by bringing advanced #CRISPR #screening services to the global R&D market. To honor ten years of groundbreaking research, we will start highlighting every week milestone CRISPR screening papers of the last decade! 🧬✨ Stay tuned! (& in the meantime, we are really keen to know about your most favorite CRISPR screening paper…)

Great keynote by Christina von Messling from Future Today Institute about pharma industry in ten year’s time. We couldn’t agree more that #syntheticbiology and #AI are two of three technologies driving the supercycle we are currently experiencing. The most optimistic future scenario predicts massively accelerated R&D experiments and a robustly structured data ecosystem in 2034 – at Vivlion we are working hard to make this come true! #CRISPRScreening #JTHOP

👏 Congratulations to the PROXIDRUGS Zukunftscluster! We are happy to announce that Vivlion will be an associated partner of the #Cluster4Future in the now approved funding period! We are looking forward to work together with the consortium and accelerate drug discovery by contributing our bioinformatic know-how. So excited to test our latest analysis pipelines with real-world data!

#PRCISR CRISPR for solute carrier (#SLC) proteins: Check out our off-the-shelve pooled libraries targeting mouse or human SLC genes. Key features of the human version: 👉 425 target genes plus essential, non-targeting and safe-harbor controls 👉 1,868 gRNAs, gene list is available 👉 4 gRNAs per gene, 1 gRNA/plasmid, lentiviral backbone, puromycin resistance 👉 skew of 1.46   Key features of the mouse version: 👉 380 target genes plus essential, non-targeting and safe-harbor controls 👉 1,670 gRNAs, gene list is available 👉 4 gRNAs per gene, 1 gRNA/plasmid, lentiviral backbone, puromycin resistance 👉 skew of 1.59   All libraries are quality-controlled and come fully sequenced, adhering to Vivlion's commitment to superior uniformity and editing efficiency to allow you to downscale your experiments. Feel free to contact us for a quote!   Solute carrier proteins constitute a large and diverse group of membrane transport proteins that facilitate the movement of a wide array of substrates across cellular membranes, including ions, nutrients, neurotransmitters and metabolic intermediates. Given their fundamental role in cellular function, SLC proteins have been implicated in a multitude of diseases, including metabolic disorders, neurological conditions and cancer.   Despite their importance, many SLC proteins remain poorly understood due to the sheer number of SLC genes – over 400 in the human genome – and the complexity of their functional roles. The PRCISR™ CRISPR SLC libraries aim to functionally zoom into SLC genes, providing a powerful tool for researchers to elucidate the specific functions and regulatory mechanisms of these proteins and their roles in various diseases.   #SoluteCarriers #SLCProteins #CRISPRscreening #SLCs #NextGenerationCRISPRscreening #TransportProteins #PERTomics

We are excited to sponsor the 2nd CRISPR Medicine Conference, happening from April 7-11 in Copenhagen, Denmark. ➡ The website is now live and registration is open. Don’t miss this fantastic opportunity to connect with the #CRISPR community! We can't wait to return to Copenhagen for science, sports (join us for our #FunRun) and networking. In the meantime, contact us for all your #CRISPRscreening needs – we are happy to help! #CRISPRMED25 #FunctionalGenomics

Interesting interview by Fiona Behan PhD, GSK’s scientific director of target discovery, on combinatorial #CRISPR screens as powerful discovery tool. We couldn’t agree more to the fact that ➡ combinatorial CRISPR screening identifies complex dependencies/vulnerabilities in cancer ➡ sophisticated AI/ML approaches are needed to full reap the wealth of data generated by combinatorial screens ➡ thorough validation processes for identified targets are key to forwarding screening hits to the clinic At Vivlion, we aim to bring combinatorial CRISPR screening and analysis tools into every target discovery pipeline. Our multiplex CRISPR libraries can be tailored to any project needs and come in any dimension and format (all-by-all or fixed gene combinations). Regardless if you are a novice to combinatorial CRISPR screening or looking for a reliable partnership for your screening and analysis needs – do not hesitate to reach out and discuss your project with us! #PRCISR #CRISPR #mpxCRISPR #SyntheticGenes #targetdiscovery

To all #Ubiquitin, #UPS, #Proteasome and #TPD enthusiasts: We now offer a comprehensive human UPS #CRISPR library as part of our off-the-shelve portfolio at Vivlion. Key features: 👉 851 genes, essential, non-targeting and safe-harbor controls, 👉 total 3,416 gRNAs, gene list is available 👉 skew of 2.61  Don’t hesitate to reach out for a quote!   The utility of this type of library has only recently been proven in the discovery of a new modality in targeted protein degradation (#TPD), published in Nature (Hsia et al., 2024): An international research team led by Alessio Ciulli (CeTPD, University Dundee) and Georg Winter (CeMM, Vienna) , together with Manuel Kaulich, Martin Wegner, Dr. Dipl.-Bioinf., Koraljka Husnjak, and Ivan Đikić from Goethe University Frankfurt, defined the mode of action of a new class of bifunctional degraders termed intramolecular bivalent #glues (IBG) – a milestone in the field. They i.a. conducted a pooled #CRISPR screen utilizing #PRCISR technology to unravel IBG1’s mode of action.

Interesting publication of McCarthy et al. presenting a theory for high-throughput genetic interaction screens utilizing unique spectral barcodes for facilitating multiplexing. The elucidation of genetic interactions surely has been one of the holy grails of functional genomics. However, we do disagree with the notion that probing genetic interaction has been limited to about 100 pre-selected gene combinations in mammalian cells. Vivlion’s #multiplex dual gRNA technology has boosted the search space and now enables all-by-all combinations of two gene pools of arbitrary sizes. What can we provide? For example, using Vivlion’s #PRCISR platform, Diehl et al. (Nucleic Acids Res 2021) screened 12,736 autophagy gene combinations with 247,032 paired gRNAs for viability in reporter-based enrichment screens. They identified over 1,570 essential genetic interactions for #autophagy flux, including interactions among paralogous genes.   Reach out if you wish to learn more about our multiplex solutions in #CRISPRscreening!