SepDetect: theory
The field of synthetic biology is defined by taking an engineering approach to biology: we identify the simplest functional parts and combine them into a complex system that carries out a desired function. This is analogous to taking electrical components and using them to make a computer.
Therasis has used synthetic and molecular biology techniques along with an industry-leading understanding of gene regulation to produce its flagship product: SepDetect. This test is able to accurately identify the presence of two biomarkers in human blood, at concentrations only found in septic patients. All it requires is one drop of blood from a patient.
The technology
Therasis started by developing a genetic construct of three key genes embedded on a test swab: on the far right is a luminescence gene. Under the right conditions, this will be transcribed into mRNA, which will be translated into a protein that will fluoresce: this is the output of the test. However, this behaviour is highly dependant on two other genes: a repressor, and an activator.
Normal patients
Normal patients have elevated levels of neither procalcitonin (PCT) or sTREM-1 in their blood, How does SepDetect communicate this with clinicians? The repressor gene constitutively (ie constantly) expresses a repressor protein. This means that it binds to the luminescence gene and prevents the latter from being bound by a polymerase enzyme- as this is the organelle (molecular machine) responsible for transcribing the gene into genetic content (mRNA) from which the functional protein is produced, we observe no fluorescence- a false result.
Infected patients
Patients with infections sometimes have an increased concentration of PCT (represented by the red protein X) in their blood. This is able to bind to the repressor protein if it is present in the blood sample above pathological concentrations, and inactivate it. The former is now unable to bind to the luminescence gene, and therefore no longer prevents transcription of the fluorescent protein.
However, research indicates that elevated PCT levels in isolation are not a good marker of sepsis, and SepDetect knows this. For this reason, even though the repression on the luminescent gene is lifted, it will still not be translated into biologically active protein, again resulting in no fluorescence, ie a negative result.
Septic patients
In the blood of septic patients, two key biomarkers are found at high concentration. As mentioned above, the presence of procalcitonin at pathological levels (those known to be only found in cases of sepsis) results in the binding and deactivation of the repressor protein. The other is sTREM-1 (represented by the green protein Y). In a similar fashion, only if this is present at septic levels in the patient's blood sample will this bind the constitutively expressed activator protein.
The resulting activator protein-sTREM-1 complex will bind to the luminescence gene and act as a positive transcription factor, encouraging RNA polymerases to bind and transcribe it into mRNA: from this, biologically active luminescent protein will be produced by the ribosome through the process of translation. Our proprietary testing machine, Tesla, will observe fluorescence and confirm a positive result for sepsis.