Information propagation by sequence-specific, template-catalyzed molecular assembly is a key motif facilitating life’s biochemical complexity, allowing the production of
thousands of sequence-defined proteins from only 20 distinct building blocks. By contrast, exploitation of catalytic templating is rare in non-biological contexts, particularly
in enzyme-free environments, where even the template-catalyzed formation of dimers is challenging. The main obstacle is product inhibition: the tendency of products to bind to templates more strongly than individual monomers, preventing catalytic turnover. We present a rationally designed enzyme-free system in which a DNA template
catalyzes, with weak product inhibition, the production of sequence-specific DNA dimers. We demonstrate selective templating of 9 different dimers with high specificity and catalytic turnover; we then show that the products can participate in downstream reactions, and that the dimerization can be coupled to covalent bond formation. Most importantly, our mechanism demonstrates a rational design principle for engineering information propagation by molecular templating.