Our technology employs a two-component strategy to target VEGF directly
to the heart. The first component is a DNA nanostructure in the shape of
a cube. We designed the nanostructure using the DNA origami technique
pioneered by the Rothemund Lab at the California Institute of
Technology. This nanostructure contains a lid that is closed shut by DNA
duplexes, which function as "locks." They are configured in such a way
that when a DNA "key strand" with a complementary sequence comes into
contact with the "lock," one of the strands is displaced and the lid
opens. We target these structures directly to the myocardium using a
second component, the targeting complex. This complex consists of an
antibody to a myocardiocyte specific marker (the cell surface protein
N-cadherin) conjugated to a biotinylated DNA "key" strand. These two motifs
are connected by a specifically engineered streptavidin-protein A chimer
that is synthesized using the pET expression system in the E. coli
strain BL(DE3). Together, these two components ensure that the release
of VEGF from the DNA nanostructures is concentrated the damaged
myocardium.