Challenge

Pharmacological therapy usually includes only a single or few therapeutics to treat the selected pathology, such as an infection, cancer or inflammation (Walsh, 2010). After application of pharmacological therapy medicine relies on the body’s own ability to heal and regenerate. With advances in medical research, we have unraveled biochemical pathways governing different stages of diseases. We now understand the role of growth factors and other endogenous mediators in the regeneration and healing processes. Often a defined temporal sequence of different factors is required for the best therapeutic effect however they are very seldom used in current medicine.

Some biopharmaceuticals used in therapy have side effects that range from mild to serious, sometimes requiring discontinuation or modification of therapy. For example the systemic inhibition of tumor necrosis factor-alpha used to treat arthritis may increase the risk of infection, the application of interferon alpha for treatment of hepatitis C infection causes nausea, and some biological drugs may promote hepatic dysfunction or have other serious side effects.

An additional important aspect connected to the application of biological drugs is the high cost of therapy. The annual cost of biological therapy for rheumatoid arthritis ranges from 15,000 – 25,000 dollars for a single patient in comparison to nonbiologic therapy cost of 100 – 300 dollars per patient per year. Treatment of hepatitis C with biologics costs from 6,000 – 15,000 dollars per year and for some other diseases the cost may exceed 100,000 dollars, which is out of reach of most patients, even in wealthy countries.

Many biopharmaceutical proteins are expressed in bacterial systems, which can be excellent producers; however bacterial endotoxins must be thoroughly removed before the administration to patients as even picomolar concentrations of an endotoxin may activate immune cells. In the production of biologics, downstream processing and formulation of the drug is very demanding. For example, the (komentar: točno katera? The first?) interferon alpha formulation was found to oxidize at room temperature, which affected its tertiary structure, decreasing its effectiveness and raising the immune response to the modified protein. The formulation and storage procedures had to be optimized to reduce antibody formation. Similar post-manufacturing structural changes have been implicated in other immune-mediated responses to recombinant proteins (Purcell et al., 2008).

Opportunities for synthetic biology in medical therapy

Figure 1. Engineered therapeutic mammalian cells can respond to specific signals by the production of desired therapeutics.