Nanosheets or nanoclusters of aminopropyl-functionalized magnesium phyllosilicate (AMP) were prepared in water by exfoliation and used as structural building blocks for the preparation of DNA-based hybrid nanostructures in the form of ordered mesolamellar nanocomposites or highly elongated nanowires, respectively. The former consisted of alternating layers of single sheets of AMP interspaced with intercalated monolayers of intact double-stranded DNA molecules of relatively short length ( approximately 700 base pairs) that were accessible to small molecules such as ethidium bromide. In contrast, the nanowires comprised isolated micrometer-long molecules of lambda-DNA or plasmid DNA that were sheathed in an ultrathin organoclay layer and which were either protected from or remained accessible to endonuclease-mediated clipping depending on the extent of biomolecule wrapping. Both types of hybrid nanostructures showed a marked increase in the DNA melting (denaturation) temperature, indicating significant thermal stabilization of the confined biomolecules. Our results suggest that nanoscale building blocks derived from organically modified inorganic clays could be useful agents for enhancing the chemical, thermal, and mechanical stability of isolated molecules or ensembles of DNA. Such constructs should have increased potential as functional components in bionanotechnology and nonviral gene transfection.