Project Description

In 2015, over 300,000 women died during pregnancy and childbirth; 99% of these deaths occurred in developing countries. Postpartum hemorrhage (PPH), or severe bleeding after birth, is the leading cause of maternal mortality worldwide. Oxytocin is a naturally occurring hormone and a medication that is used to increase contractions in the uterus (i.e., induce labor). It has also proved effective in significantly reducing the risk of PPH. Oxytocin is now routinely used in industrialized countries, and is often given in small doses simply as a preventative measure in normal labors. However, oxytocin is not readily available in developing countries. Despite being on the World Health Organization’s List of Essential Medicines for developing countries and being relatively inexpensive (as of 2014, the wholesale cost of the medication is US$0.1–0.56 per dose), oxytocin requires storage at between 2 and 8 °C, which has led to a shortage of this critical drug in rural areas that lack reliable refrigeration, power, and infrastructure. Quality issues with existing oxytocin inventories have also been identified as a significant issue in rural areas. Our first goal is to build an oxytocin detection system using a G-protein coupled receptor in yeast that will allow us to verify the presence of active oxytocin. If successful, we will then focus our efforts on synthesizing oxytocin in various forms to increase its availability in resource-poor areas. Oxytocin is produced in the body by the OXT gene. It is synthesized as an inactive precursor peptide along with its carrier molecule neurophysin I. After several iterations of hydrolyzation via enzymes, the active oxytocin molecule is produced. In 2013 an iGEM team from Lethbridge Canada created a form of oxytocin still attached to its carrier molecule, neurophysin I, which prevents degradation until the carrier molecule is cleaved resulting in the activation of the oxytocin molecule. Our team plans to significantly build on this prior work by exploring several other approaches to improving the stability of oxytocin including producing a powdered form of the drug that can be activated using hydrolysis, adding trace metals to prevent oxidation, and using optogenetic techniques to activate oxytocin using light. In addition to these synthetic biology approaches, the diversity of our team’s skills will allow us to explore several mechanical and hardware solutions including simple, non-refrigerated single-injection systems; biological packaging solutions to prevent oxytocin’s degradation; and testing systems to evaluate the quality and effectiveness of current oxytocin inventories. The solutions we plan to explore will target practices ranging from manufacturing, transportation and storage, and distribution to drug administration protocols, drug quality monitoring and control, and improved documentation and inventory to support further research and quality care.The potential impact of any and all of these solutions will be to increase the availability of oxytocin for use in under-resourced maternity facilities.

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