Capsid Engineering

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Compartmentalization defines life on earth. Considerable research has been directed towards constructing non-natural encapsulation systems such as droplets, liposomes, polymersomes, etc. to mimic natural systems and for advanced applications like drug delivery, catalysis and bioimaging. However, the size of such compartments is limited by the current microfabrication techniques ranging from tens of nanometers to a few hundred micrometers.

Natural cage-like structures (capsids) formed of some bacterial and viral proteins are interesting alternatives for compartmentalization; with the added advantage of having atomic control on the cage structure and dynamics. To enable specific encapsulation of cargo proteins in vitro and in vivo within capsids, we recently developed a general electrostatic tagging system. The capsid-forming enzyme lumazine synthase was engineered to have a negatively charged interior and cargo proteins were appended with a positively charged tag. The engineered capsid was later evolved in the laboratory to protect cells against the deleterious effects of a toxic protein (HIV protease) bearing a complementary tag.

Novel strategies for encapsulating two or more enzymes simultaneously, and other guests such as nanoparticles and drug molecules within the capsid are currently being investigated. Capsids filled with multiple enzymes will essentially function as nanoreactors in vitro or organelles in vivo, and thus have applications in nanotechnology and synthetic biology. Encapsulation of cargo and its controlled release is also being studied using other non-natural capsids. The dynamics of capsid formation is being probed in depth for enhanced protein encapsulation using various biochemical and biophysical assays.

 
 
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16.08.2017
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