Programmable DNA Hairpin Locker: Dual-Layer Encrypted Carrier Communication.

Abstract

Communication plays a crucial role in advancing human civilization, yet ensuring the confidentiality and integrity of transmitted signals remains a critical challenge. In this context, DNA represents a paradigm-shifting medium owing to its molecular programmability, ultrahigh information density, and native biocompatibility. Building on these advantages, we integrate lambda exonuclease (Exo λ) to harness DNA's programmability for constructing molecular beacon architectures, enabling precise signal recognition and processing in molecular communication systems. We developed a DNA-based dual-layer encrypted carrier communication system through modular molecular programming, supporting precise signal modulation, demodulation, and secure signal transmission. The system's core innovation is the DNA hairpin locker (DHL), an Exo λ-resistant architecture that dynamically responds to DNA signals while maintaining stable operation (with input/output orthogonality), forming our prototype molecular communication platform. To accommodate diverse modulation needs, we engineered three allosteric DHL variants supporting nine distinct input/output configurations. Additionally, we implemented a binary data-block unit and a codebook translation protocol to enhance security and extensibility. Anti-interference analysis and mitigation strategies ensure a robust system operation. This DHL-based architecture, with its programmable and modular features, provides a reliable molecular communication strategy and shows promising potential for applications in biosensing and synthetic biology.