Future Plan

The brain-storming and designing levels of our project have been implemented considering their prospective application possibilities. In the design process, probable issues regarding the ethical aspect, termination, monitoring, application technique and side effects of our treatment have also been taken into account. Discussions regarding the modularity of our parts and project have also taken place.

From these aspects, we can separate future plans of “Change of Heart” into six categories:

1. How To Apply It

• As we aim to modify our own body cells, a way to implant this new designed “familiar” cell into our cellular environment is a must. New scientific approaches and fields have been proposed, widening our perspective and allowing us to acquire possible application methods. Gene therapy and tissue engineering are two of these approaches.

• Gene therapy, along with cell therapy industry, has a variety of practicing techniques and gives us the opportunity to tune in with how long the modified gene is able to survive in our engineered cells. Gene therapy uses the techniques from plasmid transfection to genome editing. This is a clear reminder of how the route of application affects what we receive for the treatment. According to the length of duration our modified sequences stay within the cell, it is impossible to determine the consequences of this treatment in terms of cancer formation or genetic mutation. It should also be noted that gene therapy is home to some ethical issues which will be discussed later in this section.
• On the other hand, tissue engineering is another field which is related to our project. It includes the principles of constructing a tissue or sometimes a complete organ in vitro, maturing it enough to ensure that it is able to survive inside the body as well as re-implementing the tissue been built by the body’s own cells and regulating its biologic activity from outside until it adapts to the conditions inside. In vitro process may also use the benefits of synthetic biology by modifying the body cells and architecting the tissue via using these new cells. Nevertheless, despite the promising nature of this process, tissue engineering is still in need of development in order to be regarded as a serious clinical option.

2. Termination of Treatment

• For a clinician, allowing full control over the management of treatment is very important and sometimes vital. The nature of pharmacology obliges to embrace the information of how a drug diffuses through the body, its metabolism, excretion and what kind of side effects it has a possibility of generating. In some cases, the termination of treatment is a must to protect the patient’s life; therefore in the course of proposing a novel treatment, addressing such a utility can be critical.

• In our system, the treatment can be taken under control by giving simple drugs such as antibiotics. Our double plasmid system can be inhibited with the presence of tetracycline antibiotics in the media. Tetracycline is a commonly used antibiotic against intracellular microorganisms such as chlamydia and rickettsia. To transfect our vessel cells, we use pTRE vector which includes the tetracycline response element (TetRE) site compatible with tetracycline molecule. TetRE decreases the transcription rate of its related operon, in our case, hypoxia-ROS sensing promoters. With the addition of enough dose of tetracycline, the course of treatment can be controlled during the application period of synthetic plasmid devices. Because of the degradation rate of synthetic cells and devices, this termination ability of our system can prevent unnecessary and unwilling consequences of our treatment.

3. Monitoring Capability

• The determination of continuing or terminating the treatment can be conducted by well monitoring and case management. Because of the limiting nature of knowing how the cell would behave in the unpredictable cellular media, we have to add a system that will allow us to monitor the efficiency and the duration of our treatment.

• To do this, we have researched and discussed the possible applications. As it is the most relied method to monitor such treatments in clinic, we chose to conduct a system related with the biochemistry blood profile and tests. Our cells will synthesize an additional chemical compound constitutively which is not metabolized, toxic or interfere with the physiological reactions in our body. This product must also be excreted easily.
• Therefore we have considered that “inulin” can be produced within the cell by synthesizing the required enzymes presenting in the production pathway. The blood level of inulin and the increases/decreases of this level will give hints to a clinician about the course of our treatment.This method also makes it possible to determine whether the termination of our treatment has been a success by measuring if the inulin level has reached zero.

4. Side Effects and Management

• Drug interference and drug side effects are two related and important features in practical medicine. As we are targeting ischemic conditions, the drugs being produced by our synthetic cells can cause such effects or interferences especially in those who take other medications due to unrelated medical conditions or reasons. Hence we would like to foresee what kind of reactions and interferences may occur and to warn related stakeholders on the effects who are a part of this topic and project. This feature also shapes the reason why we research in depth regarding the monitoring and termination features.
• Tissue plasminogen activator (tPA) is actually a blood thinner which may interact with other oral blood thinners being administered in especially old patients because of other heart diseases or vascular problems. As our treatment approach is local effective and directed to only clot formation in heart vessels, it does not cover other mentioned conditions. Therefore, such interference may occur and must be taken serious care.
• The possible side effects cannot be predicted; hence they should be tested carefully in the future.

5. Ethical Issues

• When genetic engineering is involved in medical practices, some ethical issues may arise such as having the possibility of changing the course of original gene behaviors, triggering cancer formation or simply misusage. Another serious issue is the release of genetically modified cells into our own body environment and the possible effects of this are still unknown. Moreover, manipulating our own genomic background must be addressed in terms of being right or logical.
• An additional and specific question is whether we are able to predict how this treatment will affect our eating behavior. In the case of successful protection against heart diseases related with excessive body weight and impaired fat metabolism, would this treatment cause uncontrolled and unbalanced nourishment or widespread obesity cases? We have to address and discuss such questions and determine how we can mature the general course of our approach.

6. Modularity

• Lastly, our system proposes a modular and interchangeable device for prospective researches or approaches. Our activist proteins can be replaced with other targeting drugs for different diseases or conditions under our hypoxia sensors like cancer treatment or sepsis management. Additionally, our sensor systems like ODD peptide can be used for different objectives like extending the activity duration of specific enzymes or the inhibition of proteasome degradation pathway.
• Modularity feature is quite important regarding its ability for encouraging the conduction of novel projects or ideas, maturing old systems or updating the on-going studies.