Team:VIT Vellore

In Vivo Drug Factory

Controlled drug release, especially sustained release formulations are a major area of current research in the Health Sciences. We propose a novel approach to the problem of sustained drug release, controlled using the concentrations of the target molecule itself or associated markers – using synthetic biology.
We propose an in vivo Drug Factory (IVDF) which involves the usage of natural intestinal flora, in our case Escherichia coli, which have been genetically modified to produce a protein which is of therapeutic value to the consumer. We aim to engineer two major safety features into this model, firstly the inclusion of a hok/sok post-segregational killing mechanism in case of plasmid loss during replication – hence ensuring that growth of bacteria without plasmids is minimized. Secondly, the inclusion of a ‘kill-switch’ – using bacteriophage holins ensures that in the unlikely case of any adverse drug reactions, the production can be shut off completely.
We have chosen lactose intolerance as the disease for our pilot study, due to it's high prevalence, especially in certain parts of the world, and also because it needs the production of a well characterized protein, namely β-galactosidase.
Our system could be potentially used in the treatment of various other inborn errors of metabolism, when coupled with the appropriate promoter. Also, it would enable successful treatment of diseases such as diabetes mellitus, which otherwise is highly dependent on patient compliance.