Delivery of protein extracellularly

Abstract

The described technology pertains to biotechnology, specifically engineered bacterial systems designed for extracellular delivery of therapeutic proteins in cancer treatment. The disclosed bacteria, such as Salmonella typhimurium, are genetically modified to include plasmid coding for a therapeutic protein, a salicylic acid-inducible promoter operably linked to a lysis protein, and a plasmid retention mechanism. These bacteria are modified to remain extracellular by incorporating knockouts such as flhD, which prevent intracellular invasion of cancer cells. Upon induction with salicylic acid, the bacteria lyse and release therapeutic proteins, such as IFNγ, into the tumor microenvironment, converting the environment from immunosuppressive to immunostimulatory and reducing tumor growth. The system is designed to provide safe and tumor-specific delivery, minimizing systemic toxicity. Applications include treating solid tumors, such as pancreatic and breast cancer.

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