The engineering of genetic circuits with predictive functionality in living cells represents a defining focus of the expanding field of synthetic bioloy. Since the original toggle switch and oscillator designs, genetic circuits have been constructed that control cellular population growth, detect edges in an image, and count discrete cellular events. One promising application of genetic circuits is to program an organism to act as an intelligent sensing and delivery device to destroy malignant cells inside the human body. Although bacterial therapies have been used to treat cancer, they have met with limited success because their inherent overgrowth and toxicity, inability to penetrate tumor environments, and specificity are challenging issues to overcome. Here, we propose to use bacterial minicells as delivery vehicles that utilize synthetic gene circuitry to selectively deliver cargo to cancer cell. Minicells are spherical nanoparticles that are produced from aberrant cell divisions in bacteria and contain no chromosome. They are able to maintain plasmids, produce energy, consume oxygen, transcribe and translate DNA, but importantly they are not able to grow and divide. Therefore, minicells can be engineered to employ intelligent decision-making by sensing the environment and delivering therapeutics in-vivo while the avoiding the efficacy issues associated with live bacterial vectors.
Minicells offer a promising technology for cancer therapeutics at the interface between live cells and nanoparticles. They can be manipulated by powerful genetic engineering techniques and still maintain advantages of nanoparticle size. Thus minicells offer a unique platform to tackle specificity, targeting, cost and effectiveness of cance therapies.
