Studying genetic material to control the two-and threedimensional packing of biomolecular-scale building blocks into well-defined meso-and macroscopic structures is useful for understanding the mechanisms involved in living organisms, and assists application in biotechnology, nanotechnology, and materials chemistry.[1] Meters of genetic material are naturally packed into compact structures by a variety of methods that are optimized for specific requirements. [2,3] Although many forms of counterion-induced DNA liquid crystals (LCs), such as chiral nematic, uniaxial columnar, and higher-ordered columnar phases, [4][5][6][7][8][9] as well as supramolecular-directed DNA LCs with lamellar and columnar phases, [10][11][12] have been studied extensively, the packing behavior of DNA in vivo is not fully understood, and structures mimicking silica mineralization in vitro remain unresolved.Herein we report the synthesis of a DNA-silica complex (DSC) with a rare two-dimensional (2D) square p4mm structure (hereafter denoted p4mm), together with a new approach for the structural analysis of DNA liquid-crystal templated mesophases by electron microscopy. By exploiting the cooperative effects of a quaternary ammonium silane, which acts both as a DNA condensing agent through the positively charged quaternary ammonium group and stabilizes silica mineralization by co-condensing with the silica source, p4mm and 2D hexagonal p6mm DSCs were synthesized at different DNA concentrations, giving rise to a new DNA LC phase diagram. According to the results of simulations based on Kornyshev-Leikin theory [13,14] and previous reports on cation-crystallized DNA, [9,15,16] the small interaxial separation of about 25 formed upon quaternary ammonium phosphate electrostatic "zipping" along the DNA-DNA contacts and the silica wall formed between DNA strands in diagonal positions are considered to be optimal for formation of the p4mm structure.In general, DNA is not capable of directing surface deposition of silica to form a DNA-silica complex because silicate is negatively charged in the pH range of 4.3-11.9 needed to maintain the double-helix configuration of DNA.[17] Here we attempted to synthesize a DSC by using the cooperative effects of N-trimethoxysilylpropyl-N,N,Ntrimethylammonium chloride (TMAPS).[18] The positively charged quaternary ammonium group acts as a condensing agent for DNA, and the silane site is co-condensed with a silica source, for example, tetraethoxysilane (TEOS), for subsequent assembly of the silica framework. The trimethylene groups of TMAPS covalently tether the silicon atoms incorporated into the framework to the cationic ammonium groups regardless of the type of charge on the silicate. We investigated the packing behavior of DNA in DSCs by varying both the DNA concentration and the TMAPS/DNA molar ratio under ambient conditions of neutral pH and room temperature, and we found that varying these parameters allows the DNA interaxial separation to be controlled and consequently promotes formation of various LC phases (v...