The Problem
Antimicrobial resistance is on the rise and the death toll from bacterial infections will continue to increase if no alternative solutions are developed. The threat of antimicrobial resistance has been known for a long time - Alexander Fleming, the discoverer of penicillin, predicted in 1945 that “exposing […] microbes to nonlethal quantities of the drug makes them resistant”. Even though efforts for development of novel antimicrobial compounds have been stepped up in recent years, there is still a lack of safe and effective substitutes for antibiotics1. A promising alternative – phage therapy – has an extensive history of successful application in countries with limited access to antibiotics. Although phage therapy has been known for almost a century, widespread application of phage therapy still has to become reality.2 This was the overarching problem our project needed to tackle.
In order to design an impactful project for this year’s iGEM season, we deemed it important to precisely understand and define the problem we wanted to work on.
Through extensive research into the factors impeding phage therapy, we identified the production process to be one of the most striking problems. In particular, the current methods are inefficient, lead to high impurities and contamination, require the cultivation of human pathogens in large quantities and causes regulatory problems due to imprecise manufacturing standards and a lack of adequate quality controls.
The Solution: Phactory
We contemplated ways to use synthetic biology to overcome these challenges and found that using cell extract as the central component of a manufacturing pipeline for phages might allow us to overcome these issues. With the central piece of our project in place, we were able to define the individual modules of our manufacturing pipeline. The modular approach allowed us to break down the overall problem into several isolated, solvable sub-problems that could be worked on in parallel. For each module we defined the requirements we wanted to fulfill and brainstormed potential solutions for reaching these requirements. The individual modules were designed in such a way that they are truly independent of one another and that issues in one module would not impede progress in another module. We defined quantitative criteria to measure progress in achieving the identified requirements during the build-test cycle. To maximize our chances of success and the robustness of our designs, we chose the simplest solutions we could come up with. We defined additional goals when multiple solutions fulfilling these criteria were available: accessibility, portability, affordability, and safety.
Phactory was designed to be an accessible manufacturing pipeline that produces pure, precisely defined bacteriophages at medically relevant concentrations using highly portable, affordable and modular components.
