In the following is described the combination of straight biochemical and organic routes to graft nucleotide sequences to a chitosan backbone. The resulting chitosan-g-ssDNA hybrid self-assembles into submicrometer size structures in dilute aqueous solution as assessed by atomic force and electron microscopy imaging. The hypothesis of self-assembly driven by chemical incompatibility between the amphiphilic chitosan and nucleic acid grafts is supported further by stability of the self-assembly against ionic strength and pH variations. (C) 2015 Elsevier Ltd. All rights reserved.