Structure‐Activity Relationships in Nucleic‐Acid‐Templated Vectors Based on Peptidic Dynamic Covalent Polymers

The use of nucleic acids as templates, which can trigger the self‐assembly of their own vectors represent an emerging, simple and versatile, approach toward the self‐fabrication of tailored nucleic acids delivery vectors. However, the structure‐activity relationships governing this complex templated self‐assembly process that accompanies the complexation of nucleic acids remains poorly understood. Herein, the class of arginine‐rich dynamic covalent polymers (DCPs) composed of different monomers varying the number and position of arginines were studied. The combinations that lead to nucleic acid complexation, in saline buffer, using different templates, from short siRNA to long DNA, are described. Finally, a successful peptidic DCP featuring six‐arginine repeating unit that promote the safe and effective delivery of siRNA in live cancer cells was identified.