Prime Editing in Real World Model Systems

Prime editing is reshaping precision genome engineering by enabling targeted substitutions, small insertions, and deletions without requiring double-strand breaks or donor DNA templates. Yet much of what the field considers “optimized” performance has been established in model-friendly settings—immortalized mammalian cell lines, a limited set of tractable microbes, and a handful of laboratory plant and animal models—where delivery is routine, screening is efficient, and validation pipelines are mature. In contrast, the next wave of impact for prime editing depends on its reliability in systems that are not built for genetic manipulation: non-model organisms, hard-to-transfect or hard-to-regenerate tissues, complex genomes, and real-world contexts in which selection markers, clonal isolation, or repeated rounds of optimization are impractical.This Research Topic, “Prime Editing Beyond ‘Model-friendly’ Systems,” will highlight advances that adapt prime editing to diverse biological and technical landscapes, and will clarify how differences in DNA repair capacity, cell cycle state, chromatin context, genome architecture, and organismal physiology shape editing outcomes. We welcome studies that extend prime editing into non-standard experimental platforms, including primary cells, organoids, differentiated tissues, and in vivo contexts, as well as non-model animals, plants, fungi, parasites, and environmentally or industrially relevant microbes. Submissions that address delivery barriers are particularly encouraged, including viral and non-viral approaches, dual-vector or compact editor strategies, RNA- or RNP-based delivery, electroporation or microinjection workflows, and methods that improve tissue targeting, biodistribution, and dose control.A core aim of the collection is to move beyond headline efficiency values and toward deeper, system-specific characterization of edit quality. Contributions that quantify product purity, byproduct spectra, unintended edits, and larger structural outcomes—supported by robust genotyping, long-read sequencing, or standardized computational pipelines—are strongly encouraged. We also invite work that proposes reproducible design and reporting practices for pegRNAs, target site selection, and outcome analysis, enabling meaningful comparisons across organisms and laboratories. By integrating mechanistic insight with practical engineering, this collection seeks to establish clearer principles for prime editing in challenging systems, expand access to precision editing across biological diversity, and accelerate translation into agriculture, biomanufacturing, and therapeutically relevant tissues where model-friendly assumptions do not hold. Topic editors: Zaneta Matuszek, Sivabalan Karthik, JAE BOK HEO Source: https://www.frontiersin.org/research-topics/80096/prime-editing-in-real-world-model-systems