Multifunctional Artificial Immunoengineering (MAI): A Foundational Framework for Next-Generation Hybrid Immunomodulatory Constructs with In-Construct Biocomputation

This manuscript introduces Multifunctional Artificial Immunoengineering (MAI), a pioneering interdisciplinary framework that fuses synthetic biology, systems immunology, nanoscale engineering, computational immunodynamics, adaptive control, self-assembly, reinforcement learning, biocompatibility design, and in-construct biocomputation to create hybrid intelligent immunomodulatory constructs (HIMCs). HIMCs function as autonomous, multi-role immune sentinels, delivering polychronic polyfunctionality, reactive nanoporosity, optimized renal clearance, autoimmunity-aware regulation, and embedded DNA/ribozyme logic for real-time decision-making and quantized effector release.Grounded in seven core pillars—from polyfunctional binding thermodynamics to nanoscale disassembly and biocomputation theory—the framework addresses limitations of monofunctional immunotherapies by enabling dynamic threat response to pathogens and cancer. Key theoretical models include a coupled immunodynamic PDE system for spatiotemporal simulations, autoimmunity-penalized reinforcement learning for adaptive control, and variance-based global sensitivity analysis (GSA) for robustness calibration.Methodologies encompass epitope mapping via cryo-EM and AlphaFold, Rosetta-optimized assembly, RL training on GPU clusters, and validation techniques like smFRET for release profiling. In silico results demonstrate rapid pathogen clearance (e.g., 4.9–12.4 hours for diverse strains), near-complete CRS risk mitigation (0.3% incidence), 97.3% DNA logic fidelity, and tumor volume regression to 12.7% of baseline within 14 days, outperforming controls.The discussion highlights MAI's adaptivity, safety, and autonomy, extending DNA origami applications while outlining a 15-year translational roadmap to FDA/EMA approval and cost reductions to $180/dose. Ethical safeguards address dual-use risks, equity, and governance. As a self-contained conceptual paradigm, this work lays the foundation for next-generation immunoprotection, bridging theory to clinical potential without empirical data generation.