Engineered exosomes are emerging as biocompatible nanocarriers for delivering CRISPR/Cas components to resistant tumor cells, enabling targeted disruption of oncogenic drivers and resistance-associated pathways. Engineered exosomes offer several delivery-platform advantages, including biocompatibility, membrane-mediated cargo protection, programmable tumor targeting, and potential tissue penetration. Selection of the CRISPR modality, Cas9 ribonucleoprotein, mRNA, base editor, or prime editor, depends on payload size, stability, editing duration, endosomal escape, and nuclear delivery requirements. Therapeutically, these systems may disrupt oncogenic drivers, inhibit resistance pathways, restore tumor-suppressor activity, and re-sensitize tumors to targeted therapy, chemotherapy, or immunotherapy. Clinical translation will require scalable manufacturing, reproducible cargo loading, standardized characterization, validated potency assays, off-target control, and clearly defined regulatory pathways. The goal of this review is to outline a realistic pathway featuring proof-of-concept research, through discoveries to the creation of manufacturable, safe, and effective exosome/CRISPR therapeutics that can trigger durable therapeutic responses in resistant malignancies.
Synthetic biology has redefined the therapeutic role of microbes, transforming them from passive commensals or delivery vehicles into programmable living therapeutics capable of sensing, computing, and actuating within host tissues. This transformation is particularly relevant to metabolic disorders and oncological conditions in which pathophysiology is spatially heterogeneous, dynamically regulated and strongly modulated by host-microbe interactions. Engineered bacterial strains and other microbial platforms can be designed to degrade toxic metabolites, replace deficient enzymes or hormones, alter bile-acid and short-chain-fatty-acid profiles, modulate host immunity, and deliver antitumor payloads with spatial precision. In metabolic disorders, early live biotherapeutic programs have demonstrated that engineered Escherichia coli is capable of metabolically degrading phenylalanine in phenylketonuria, thereby providing a clinical proof of mechanism for gut-restricted metabolic interception. In oncology, tumor colonizing bacteria have been engineered to express cytokines, checkpoint inhibitors, lytic toxins, and diagnostic signals, and their application has been recently demonstrated in colorectal cancer detection and localized immunomodulation. Despite this progress, clinical translation remains limited by variable survival and functional activity in vivo, inconsistent engraftment, metabolic and genetic instability, biocontainment requirements, manufacturing complexity, and uncertain dose control, persist in biogenetic engineering. This review highlights chassis selection, circuit architectures, applications for metabolic diseases and cancer, metabolic bottlenecks, and future directions for precision microbial therapeutics.
Boniface Adakole Onoja, S. A. Agada, Waheeb S. Aggad et al.· Microbiology Research· 0 citations