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Revision as of 23:01, 26 October 2012
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Into the Mirror World: Balancing Self-Assembly with Nuclease Resistance
Abstract:
It is now possible to create fully-addressable nanostructures from hundreds of unique synthetic DNA strands. Such structures, being made of biologically-natural D-DNA, are easily degraded by nucleases, posing a potential problem for in-vivo applications such as drug delivery. The oppositely-chiral L-DNA cannot be so degraded due to the inability of chiral nucleases to recognize and attack its mirror-image structure. Unfortunately, L-DNA is currently much more expensive than D-DNA. Here we demonstrate a method for inexpensively creating L-DNA structures with controlled shapes: a repetitive L-DNA structure is templated on an inexpensive, all-unique D-DNA layer. The D-DNA layer forms first, exposing D-DNA handles at defined locations. Subsequently, alternating rows of identical L-DNA/D-DNA chimerical strands are added through hybridization of complementary handles. The D-DNA template can then be enzymatically degraded while the assembled L-DNA structure stays intact, resulting in an economical yet nuclease-resistant nanostructure.