Over the past decades, Mexico has undergone a series transformations. Wealth has increased, families are having fewer children, and there has been improved access to health care for the poor. However, its public health resources now face a growing burden from a familiar challenge: cancer, which has become the second cause of mortality.

Dr. Alejandro Mohar, Director General of the National Cancer Institute of Mexico (INCan) noted that cancer is currently the second leading cause of death in the country, with approximately 125,000 new cases each year. The latest projection is that left uncontrolled, this rate will double to 250,000 new cancer cases per year by 2030. Thus, our project aims to contribute to the various novel therapies that are being developed using a more specific method to deliver a therapy.

By harnessing the inherent ability of facultative anaerobic bacteria to colonize and grow in tumoral environments, this project aims to develop a bacterial cancer therapy. A genetically modified E. coli strain will have knockouts in the lpp and msbB genes, which encode for the Braun's lipoprotein and for the myristic acid moiety transporter of the lipopolysaccharide, respectively. These genes are known to trigger an immune response in the human body; by deleting them, the impact originating from a bacterial intravenous administration will be reduced. Furthermore, these bacteria will produce M13-modified bacteriophages under the control of a quorum sensing system. The resulting phages will be capable of binding to the GRP78 receptor, which is usually overexpressed in cancerous cells. Subsequently, they will internalize and transfect the cancerous cells with two different genes: apoptin, responsible for an apoptotic protein specific for cancerous cells which will be regulated by a constitutive promoter and a survivin siRNA. The latter will inhibit the uncontrollable growth characteristic of cancer cells, making them more vulnerable to apoptosis.