The research conducted by Otto and his research group is focused on various fields, varying from the origin of life (self-replicating systems and the Darwinian evolution thereof), to materials chemistry (self-synthesizing fibres, hydrogels and nanoparticle surfaces).
Specific interests include self-replicating molecules, foldamers, catalysis, molecular recognition of biomolecules and self-synthesizing materials (materials of which their self-assembly drives the synthesis of the molecules that assemble). The complex chemical mixtures that are designed, made and researched often display new properties that are relevant to understanding how new traits are able to arise in nature. The final goal of all of this research is the de novo synthesis of new forms of life via the integration of self-replicating systems with metabolism and compartmentalization. His 114 publications have been cited a total of 8,873 times by other scientists. His h-index is 51.