Medical Application

Therapeutic Application ≠ usage of fancy state-of-the-art methods BUT reliable simplistic methods

In Biomedical Research, only transparent and simplistic therapeutic approaches, which can be evaluated in all stages of clinical trials, will end up in the patient.

Nowadays, one of the holy grail in Synthetic Biology is a) to understand the complex regulation mechanism on (co-)transcriptional and (co-)translational networks on every imaginable level and b) to manipulate and rewire those networks.

Great efforts, especially in Computational Biology and Systems Biology, have been achieved to understand the complex homeostasis-network of life. Although many principles of regulation have been understood, only relative small networks can be modelled and simulated computationally; the outcome of a “healthy” network are sometimes well understood in this case.

BUT pathological networks, where a defective network node causes a shift in the cell/organ/organisms’ homeostasis and thus result in “disease” are poorly understood, since there are still too many unknown network nodes and/or the dynamic and impact of a node is not understood.

Consequently, the rewiring of a complex pathological network to achieve a desired outcome is even more complex due to many unknown variables; thus, it is most likely illusional to only rely on rewired genetic circuits on engineered cells to achieve healing in an individual.

Of course, it will just be a matter of time until engineered cells can sense the “problem”, to then integrate and compute it accordingly generating an output function to “solve the problem”. Unfortunately, for now this still remains science fiction.

Biologization of Technology vs. Technologization of Biology

Currently, there is a trend to solve biological and even technical problems with Biology (Biologization of Technology), especially Synthetic Biology, e.g. engineered algae fuel or solve mathematical problem (traveling salesman problem as popular example) with swarming bacteria (Myxococus) or Mycetozoa; unquestionably, those great results are of major impact to solve or understand global challenges.

But in biomedical research, it is undisputed that many challenges in healthcare cannot just be solved with biology and needs interdisciplinary help from many scientific fields for reasons, mentioned above. Many (pathological) biological networks are too poorly understood and the construction of a “rewired correction network” to compensate the misregulated homeostasis is consequently unpredictable and thus not available for human therapy. Of course there a exceptions, where fully rewired cellular systems are currently in trial for humans, e.g. usiig Chimeric Antigen Receptors (CAR) on T-cells as cancer therapeutic.

Technical solutions to human health problem are more widely available (Technologization of Biology) since this discipline exists just longer thanSynthetic Biology. The most-popular examples are fully non-biological solutions, e.g. an artificial heart, which can replaces the human heart for a long time. The reasons why this solution can be be “just technical” is that the human heart is basically just a very complicated pump. The challenges were more of fluiddynamic nature to pump our blood without destroying or clotting the cells.

But there a many medical problems which cannot be solved by just using parts of electromechanical engineering. A showcase would be glucose-resistant islet cell (one of the many forms of diabetes) which does not secrete insulin when stimulated with glucose. No non-biological solution will ever exist for this, since the only input function to bring back the dysregulated metabolism back to the physiological homeostasis is the protein insulin, an undoubtedly biological component.

A kybernetic bio-printed device to control blood glucose level

However, one can luckily combine the best of both disciplines, the reliablity and durability of electromechanical components and the ability to create simplistic bio-orthogonal signal transducer/integrator to capture the output function and translate it into a bio-compatible signal.

To remain with the above mentioned example with glucose-resistant or destroyed β-cells by autoimmune disease, one in general could bio-print (LINKLINKLINKLINKLINKLINKLINKLINKLINKLINKLINKLINKLINK click here for more on our bioprinting project) an kybernetic organ composed of a electromechanical part and a biological part. The technical part would measure the current physiological state of the body (glucose level) and will compute an output function encoded as a normally bio-orthogonal signal; only the desired printed target cells will respond to this signal (Bio-orthogonality minimizes the off-target effects compared to the usage non-bio-orthogonal signals). This signal will be integrated intracelluarly resulting in the generation of a desired biological output function to bring back or maintain the glucose homeostasis. The change is again measured by the electronic sensor which then again generates a new output function for the bio-engineered cells. The electromechanical, bio-engineered and biological parts form together a so-called closed-loop-control-circuit.

Figure1: BALBALBALBAL.

Biological Part

Technical Part

Kill two birds with one stone

Figure2: BALBALBALBAL.

Literaturreferenz

Literaturreferenz^[1]

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Links

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Bilder

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Introduction

Design

Experiments

Proof of concept

Demonstrate

Discussion

References

1. ↑ Schmidt, T. G., & Skerra, A. (2007). The Strep-tag system for one-step purification and high-affinity detection or capturing of proteins. Nature protocols, 2(6), 1528-1535.