Engineering multifunctional blood products with synthetic biology
Abstract
Engineering multifunctional blood products with synthetic biologyResearch Problem, technical approaches, anticipated outcome of the research, if successful, and impact on DoD capabilities: Platelets are blood cells that circulate throughout the body and play an important role inhomeostasis, wound healing, angiogenesis, inflammation, and clot formation ~ all of which relyupon the sufficient supply of platelets within a person~s bloodstream. During disease and injury, transfusion remains the most effective way to increase a patient~s blood platelet count, however, limitations in the supply of platelets is a constant problem because platelets have a limited shelflife of 5 days, which poses a significant challenge for maintaining sufficient supplies. Therefore,finding alternative sources of high-quality platelets can help alleviate chronic shortages in the supply of platelets. In addition to increasing platelet counts in vitro, we are utilizing synthetic biology to engineer platelets as sensing and delivery vehicles for locating injury-related trauma, and secreting therapeutic proteins to these sites to enable the stabilization of patients until they canbe transported to safety. This novel technology will also be used to stabilize soldiers who experience significant trauma, and enhanced wound healing. This approach is significant because it has the potential to produce large volumes of purified platelets that will eliminate the inherent risks associated with human donation. Based upon the need for improved tools to enhance the production of platelets in vitro, we have initiate a line of experimentation to engineer dynamic microenvironments that: (1) to control thecontribution of intrinsic cues on HSC proliferation and differentiation of platelets, (2) control theextrinsic cues on HSC proliferation and differentiation of platelets, and (3) to engineer platelets to deliver therapeutic biomolecules to sites of injury. Using synthetic biology, we propose to engineer platelet precursor cells (megakaryocytes) to package therapeutic levels of protein cargo to be targeted for platelet secretion. The synthetic biology strategies outlined in this proposal allow us to insert any genetic circuit into the genome of ES cells and differentiate them into a desired committed cell harboring that genetic circuit. This allows flexibility to put in any therapeuticbiomolecule to be expressed in differentiated cells. This approach has future naval relevance in that our approach will be used in human induced pluripotent stem cells. These cells have the potential to provide a replenishable source of on-demand, patient-matched platelets for transfusions. Moreover, it is also possible to choose universal donors of iPS cells for massproducing platelets and banking them for use in trauma scenarios. Much of the trauma seen in soldiers during conflict is a result of explosive devices, resulting in serious injury that needs immediate attention. Equipping medics with platelets for treating soldiers on the battlefield has the potential to significantly increase their survival by ~buying time~ until they can be transported to a safer location for treatment. Furthermore, the ability to load platelets with biomolecules to be delivered to sites of trauma will provide a significant advance in producing multifunctional blood products.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Sep 23, 2016
- Source ID
- N000141613012
Entities
People
- Tara L Deans
Organizations
- Office of Naval Research
- United States Navy
- University of Utah