In this presentation, Martin Wegner, Head of R&D at Vivlion, introduced PRCISR CRISPR, the company’s CRISPR-enabled discovery platform designed to improve the efficiency and scalability of functional genomic screening. Based in Frankfurt, Vivlion focuses on generating highly uniform CRISPR libraries that reduce cost, environmental impact, and experimental variability – ultimately enabling broader applications, including combinatorial and genome-wide screening.
Wegner explained that traditional plasmid libraries suffer from uneven distribution of guide RNAs, often measured by a high skew between the most and least abundant sequences. Vivlion’s proprietary method bypassed several cloning steps, replacing sequences in phage-derived single-stranded plasmids through site-directed mutagenesis. This approach significantly improved library uniformity, achieving skew values as low as 1.6 – much closer to the ideal of 1.0 – thus enabling lower coverage without sacrificing statistical confidence.
Vivlion demonstrated these advantages through collaborations, notably with Repare Therapeutics. In one study, a reengineered version of the widely used Toronto KnockOut v3 library achieved superior results at one-quarter the usual guide representation, maintaining hit identification in viability screens. This proved Vivlion’s claim that better uniformity permits significant experimental downscaling.
Wegner also described the development of their genome-wide library, comprising four empirically validated guide RNAs per gene, selected from published datasets. Compared to existing libraries, Vivlion’s version showed improved performance in essential gene dropout and overall guide RNA activity.
He introduced two advanced strategies: fixed pair (dual guides targeting one gene) and multiplexing (targeting two genes per cell), which improved editing efficiency and enabled direct combinatorial screening without the need for isogenic cell line clones. These methods support exploration of genetic interactions, such as BRCA-PARP synthetic lethality, across multiple contexts.
The talk concluded with an aspirational roadmap to build genome-wide gene interaction datasets using compressed screening strategies and iterative design informed by AI. Wegner also highlighted Vivlion’s modular services, from library design and screening to bioinformatics and consulting, all built around their core strength: high-uniformity CRISPR libraries. This technology, he argued, positioned Vivlion to lead in scalable, precise functional genomics.
