The structure of the DNA double helix first highlighted the simple elegance of the most sophisticated template reactions known, template directed polymerization. Through these reactions the genomic information is accurately replicated in DNA, transcribed into RNA, and translated into protein. Over 40 years ago, Crick combined these reactions into the "Central Dogma" of biology ( Figure 5-l), a formulation suggesting that all living things follow this basic chemical plan [ 11. Today, even with the incredible biological diversity known to exist on Earth, no violations of this chemical scheme are known. The nucleic acids store the genetic blueprint, and the co-catalytic proteins function cooperatively with this molecular template to express the encoded information.Over the last four decades, synthetic non-enzymatic oligonucleotide ligations have been explored as potential models for the evolution of replicating systems on the early Earth [2-111. These studies have explored ligation reactions that occur on a template without protein/enzymatic catalysis. Such systems have both provided mechanisms for the early evolution of biopolymer catalysts and placed limits on template directed ligation. More recently, the lure of antisense molecules capable of disrupting specific gene expression has resulted in the exploration of backbone-modified nucleic acids [ 12-33]. n