Toward predictable and programmable genetic circuits in plants

Abstract

Predictable design is central to realizing the potential of plant genetic circuits by linking regulatory architecture to phenotypic outcomes. Despite rapid advances in genetic parts and circuit construction, most plant circuits are still developed through empirical optimization, limiting their scalability, reuse, and predictability. In this review, we examine why quantitative prediction in plants remains challenging and organize recent advances within an emerging quantitative engineering framework. We discuss how genomic and epigenetic context, developmental progression, spatial organization, and environmental variability shape circuit behavior, together with strategies that move beyond qualitative switching toward quantitative sensing, information processing, and model-informed design. Achieving predictable circuit behavior will require quantitative characterization, standardized measurement, multiscale modeling, and iterative design workflows that account for cellular and physiological context. As plant synthetic biology expands from model systems toward crops and field environments, predictive performance will also depend on species-specific physiology and fluctuating environmental conditions. Automation, high-throughput phenotyping, and AI-assisted modeling will likely become increasingly important for extracting transferable design principles across biological systems and environmental conditions. Collectively, these advances position predictability in plant synthetic biology as a systems-level engineering challenge requiring coordinated quantitative design across genetic, physiological, and environmental scales.

Keywords: DBTL cycle; Plant synthetic biology; Precision genome engineering; Predictive engineering; Synthetic genetic circuits.