Molecular programming with DNA/RNA

I will discuss my lab’s research on engineering nucleic acid-based nanostructures and their applications in imaging, biosensing, nano-fabrication, and tissue engineering.

We have invented a general framework for programming the self-assembly of synthetic nucleic acid strands into prescribed target shapes or demonstrating their prescribed dynamic behavior. Using DNA, we have demonstrated the modular construction of sophisticated 1D (Science, 321:824, 2008), 2D (Nature, 485:623-626, 2012) and 3D (Science, 338:1177, 2012; Science, 334:65, 2014) structures on the 100-nanometer scale with nanometer precision. Using reconfigurable DNA hairpins, we have demonstrated diverse, dynamic behavior such as catalytic circuits, triggered assembly, and autonomous locomotion (Nature, 451:318, 2008). By interfacing these synthetic, nucleic acid nanostructures with functional molecules, we are developing diverse applications. In bioimaging, we have engineered geometrically encoded fluorescent barcodes for highly multiplexed single-molecule imaging (Nature Chemistry, 4:832-839, 2012) and dynamic fluorescent probes for highly multiplexed 3D super-resolution cellular imaging (Nature Methods, 11:313, 2014; Science, 334:65, 2014). In biosensing, we have constructed robust and ultraspecific probes for detecting single-base changes in singlestranded DNA/RNA targets (Nature Chemistry, 4:208-214, 2012). In nanofabrication, we have collaboratively developed a versatile framework for producing inorganic materials (e.g. graphene [Nature Communications, 4:1663, 2013], silicon dioxides [JACS, 135:6778, 2013], silver, gold) with arbitrarily prescribed nanometer scale shapes. In tissue engineering, we have developed a general strategy to engineer DNA directed self-assembly of biocompatible hydrogel bricks into complex architectures (Nature Communications, 4:2275, 2013).

I will also discuss engineering RNA nano-devices in living cells, in particular a RNA hairpin device that enables wide dynamic range and highly orthogonal regulation of gene expression and implements complex logic.