Nucleotide-based copying of nucleic acid sequences without enzymes.

Chemical primer extension is the enzyme-free incorporation of nucleotides at the end of an oligonucleotide, directed by a template. The reaction mimics the copying of sequences during replication but relies on recognition and reactivity of nucleic acids alone. Copying is low-yielding, particularly for long RNA. Hydrolysis of active esters and inhibition through hydrolysis products have been identified as factors that prevent high yields, and approaches to overcoming them have culminated in successful template-directed solid-phase syntheses for RNA and phosphoramidate DNA.