| dc.description.abstract | Nucleic acids serve as the molecular blueprint for all life on earth. Oligonucleotides hybridize to form the classic double helix architecture by aligning complementary bases to hydrogen bond with one another following a trivial set of rules termed Watson-Crick (WC) base pairing. WC base pairing rules state that adenine (A) residues always pair with thymine (T) residues and likewise guanine (G) residues always pair with cytidine (C) residues in the double helix conformation. This straightforward design principle is what endows nucleic acids with immense information storage capacity in order to encode life. Furthermore, this principle makes DNA a choice candidate for abiological nano-engineering. Through rational design of WC base pairing, it is possible to design limitless synthetic nucleic acid molecular architectures, both static and dynamic, with unparalleled precision. This unique feature of DNA has brought about the development of DNA nanotechnology. This area of research centers around using DNA to design dynamic as well as static nucleic acid architectures and systems with unprecedented functionality. With advances in synthesis, DNA nanotechnology has expanded to encompass all variety of modified and unmodified oligonucleotide systems capable of performing complex decision making tasks and even interacting with living systems as potential diagnostic and therapeutic tools. Despite the innovation that has come about in the past 40 years, numerous challenges remain in the application of DNA nanotechnology in vivo.
Until recently, DNA nanotechnology has remained in a predominantly homochiral paradigm. Even modified nucleobases have the naturally occurring D-stereochemistry in the ribose sugar ring. As a result, all of these polymers are subject to off target hybridization, protein interaction, and degradation. This body of work will cover structure based heterochiral interactions as well as the creation of sequence specific interactions between oligonucleotide enantiomers, a completely new phenomenon in the field of DNA nanotechnology. Heterochiral DNA nanotechnology is the study of fundamental interactions between oligonucleotides of opposing chirality, D- and L-. The utilization of L-oligonucleotides in biological systems provides several unique advantages over the natural D-stereoisomer. L-DNA/RNA cannot be degraded by native enzymes, is typically not recognized by DNA/RNA binding proteins and is incapable of forming contiguous Watson-Crick base pairs with the native D-polymer. The work herein describes the various facets in which these unique properties may be exploited to design DNA nanotechnologies using L-DNA and L-RNA. Critically, we generalize sequence specific information communication between oligonucleotides of opposite chirality, as a result, the design principles described may be applied to all existing DNA nanotechnologies. Furthermore, we expect that the application of L-nucleic acids will find broad applications in biological chemistry as a whole as we move into the future. | |
