Living drugs: A wonderful evolution for therapeutic applications

Living drugs, including engineered and natural bacteria, viruses, and immune cells, act as microscopic agents capable of precisely targeting and treating diseases, reducing side effects of conventional therapies. While many reviews address these agents individually, this work consolidates major living drug strategies by comparing their design features. We analyze bacterial, viral, and cellular therapies, emphasizing advances that improve targeting, minimize off-target effects, and overcome drug delivery challenges in early clinical trials. Drawing on preclinical studies and clinical data, we explore key genetic modifications, therapeutic payloads, and synergistic regimens. Our synthesis identifies obstacles such as immune clearance and safety risks while highlighting opportunities to improve stability and integrate co-therapies. Although strong preclinical evidence supports multiple platforms, well-designed clinical trials are essential to ensure safety, optimize efficacy, and realize the potential of these next-generation therapeutics for cancer, infectious diseases, and beyond. Living drugs represent a transformative shift in the treatment of complex diseases such as cancer and multidrug-resistant infections. Unlike conventional pharmaceuticals, these living agents—including engineered bacteria, viruses, phages, and immune cells—can sense and adapt to the biological environment, actively target diseased tissues, and deliver therapeutic payloads with unparalleled precision. This review synthesizes current strategies across these modalities, outlining the design principles and clinical progress that define the field. A key conclusion is that integrating advanced targeting, safety engineering, and combination regimens is essential for unlocking the full therapeutic potential of living drugs. Recent breakthroughs discussed in this review include synthetic biology-driven control of bacterial and viral vectors, phage engineering to overcome antibiotic resistance, and the convergence of living drugs with checkpoint inhibitors, gene therapies, and photothermal ablation for cancer treatment. Our laboratory’s development of an AUN-based cancer therapy—capable of selective tumor colonization and immune-independent vascular disruption without genetic modification—exemplifies how natural systems can be harnessed for safe, tumor-specific treatment. These advances are supported by growing regulatory pathways, improved delivery systems, and increasing public acceptance of living therapeutics. Looking ahead, living drugs could redefine the landscape of precision medicine by offering adaptive, self-regulating treatments tailored to individual disease biology. Their potential societal impact is profound: reducing dependence on long-term chemical therapies, addressing antibiotic resistance, and expanding access to effective cancer treatments worldwide. By bridging microbiology, immunology, biomaterials, and clinical science, living drugs hold the promise of reshaping healthcare into a more personalized, sustainable, and globally accessible system. Living drugs—including bacteria, viruses, yeast, protozoans, algae, and immune cells—offer precise, adaptive therapies for cancer and infections. This review consolidates design principles across bacterial, viral, and cellular platforms, highlights advances improving targeting and safety, and outlines opportunities for translation into next-generation clinical therapeutics.