Team:UCLA/Protein Cages
Introduction
Higher order self-assembling protein assemblies are commonplace in nature, such as ferritin, which carries iron in many single-celled organisms. Due to their encapsulating function and box-like structure, such assemblies are often called protein “cages.” Inspired by these natural sources, an abundance of research has been done into creating synthetic cages with new customized properties such as stability, size, and subunit types. Furthermore, while applications for cages have been suggested, many have not been tested experimentally.
An application that we have centered our project around is targeted drug delivery. By specifying the site of delivery, the effects of the drug can be limited to desired areas with maximized efficiency and we can avoid damaging undesired targets in the body.
Thrombosis, the process by which a clot forms in the blood stream, is associated with widespread diseases including stroke and many heart conditions. Anticoagulants prevent clot formation by interfering with clotting factors and allowing for smoother blood flow and restoring normal circulation. However, these drugs can have detrimental side effects, such as an inability to inhibit fatal blood loss through cuts or other wounds. By localizing the site of delivery and reducing the necessary drug dosage, we can mitigate these kinds of problems. A protein cage encapsulating an anticoagulant drug that would selectively release its payload at the site of a clot would fulfill this purpose. To specify the target, we should select an associated enzyme or byproduct of the clotting cascade. Thrombin, a protease present at blood clots, cleaves a specific amino acid sequence. This sequence, if properly inserted into a protein cage containing an anticoagulant, would result in disassembly of the cage, release of the drug molecule to the targeted area, and destruction of the clot.
