High-Throughput Screening Platforms for Editor Performance and Safety

Genome and epigenome editors—including CRISPR nucleases, base editors, prime editors, and emerging RNA/epitranscriptomic editors—are advancing rapidly, but translation is increasingly gated by measurement: How efficiently does an editor achieve the intended modification in the right cell type, and what are the full safety consequences (off-target edits, bystander effects, structural variants, chromosomal rearrangements, genotoxic stress, and unintended transcriptional or epigenetic changes)? This Research Topic will spotlight high-throughput screening platforms that make editor evaluation faster, more quantitative, and more predictive of real-world performance—moving from “single-locus validation” to scalable, systematic, and comparative assessment.We invite submissions that develop or apply next-generation assay systems to benchmark editor activity, fidelity, and downstream cellular impact across diverse genomic contexts, delivery modalities, and biologically relevant models. We particularly encourage original submissions and efforts to recruit studies spanning a broad range of editing modalities—including base editing, prime editing, epigenome editing, and related approaches—to ensure comprehensive coverage of the field’s expanding toolkit. Of particular interest are platforms that integrate automation, multiplexing, and deep readouts (NGS, long-read sequencing, single-cell multi-omics, imaging, functional phenotypes) to link editor design → cellular response → safety profile. We welcome studies that emphasize standardization, reproducibility, and interpretability, enabling cross-lab comparisons and accelerating both therapeutic and research use of editors.Key themes and welcomed contributions includes:1. Pooled and arrayed high-throughput editor screens (barcode-linked libraries, guide/editor optimization, saturation mutagenesis)2. Off-target and on-target integrity mapping at scale (including long-read and structural variant detection)3. Single-cell screening to capture heterogeneity, clonal dynamics, and rare adverse outcomes4. Functional safety endpoints: DNA damage response, p53 activation, cell fitness, differentiation, senescence, immunogenicity, and transcriptome-wide perturbations5. Model innovation: organoids, primary cells, iPSC-derived systems, microphysiological systems, and in vivo screening strategies6. Delivery-aware screening (AAV/LNP/electroporation comparisons; dose–response; exposure time; tissue-specific constraints)7. Computational pipelines and ML models for predicting efficiency and risk from sequence/context and for assay deconvolution8. Benchmarking/standards: reference materials, shared datasets, inter-lab comparisons, and best-practice reporting guidelines Topic editors: Shakil Ahmad, Valeria Palma-Onetto, Dasong Chen Source: https://www.frontiersin.org/research-topics/78304/high-throughput-screening-platforms-for-editor-performance-and-safety