Designer, Programmable DNA‐peptide hybrid materials with emergent properties to probe and modulate biological systems

Abstract

The chemistry of DNA endows it with certain functional properties that facilitate the generation of self-assembled nanostructures, offering precise control over their geometry and morphology, that can be exploited for advanced biological applications. Despite the structural promise of these materials, their applications are limited owing to lack of functional capability to interact favourably with biological systems, which has been achieved by functional proteins or peptides. Herein, we outline a strategy for functionalizing DNA structures with short-peptides, leading to the formation of DNA-peptide hybrid materials. This proposition offers the opportunity to leverage the unique advantages of each of these bio-molecules, that have far reaching emergent properties in terms of better cellular interactions and uptake, better stability in biological media, an acceptable and programmable immune response and high bioactive molecule loading capacities. We discuss the synthetic strategies for the formation of these materials, namely, solid-phase functionalization and solution-coupling functionalization. We then proceed to highlight selected biological applications of these materials in the domains of cell instruction & molecular recognition, gene delivery, drug delivery and bone & tissue regeneration. We conclude with discussions shedding light on the challenges that these materials pose and offer our insights on future directions of peptide-DNA research for targeted biomedical applications.

Structural DNA nanotechnology at the nexus of next-generation bio-applications: challenges and perspectives

“…Peptide-DNA hybrid nanotechnology could also generate new classes of articial extracellular matrices. 203 It has…”

“…Peptide-DNA hybrid nanotechnology could also generate new classes of artificial extracellular matrices. 203 It has recently been shown that ex vivo cellular scaffolding on which human cervical cancer cells attach robustly, live, and survive with high migration rates, may be produced using the combination of peptide and DNA nanotechnology.…”

From tensegrity to human organs-on-chips: implications for mechanobiology and mechanotherapeutics

“…adhesive receptor ligands) along their surface in defined positions and densities with nanometer precision that can provide ways to control cell behaviors [ 79 ]. They also can be combined with peptides to create 3D hybrid scaffold materials for various medical applications, including tissue regeneration [ 80 ]. Interestingly, tensegrity principles are often used to design these self assembled DNAs to produce stable 3D structures and desired mechanical responsiveness [ 81 , 82 ].…”

DNA functionalized programmable hybrid biomaterials for targeted multiplexed applications

“…DNA-based hybrid materials constructed by combining DNA with other materials, such as polymers, metallic nanoparticles, peptides, and inorganic compounds, have attracted significant attention in the field of biological engineering. [22][23][24] Combining DNA with other materials confers additional functionalities to the already large repertoire of capabilities that DNA demonstrates. [25][26][27] The advancement of DNA nanotechnology and the limitless possibility to combine DNA with a wide array of functional materials have opened a broad and innovative area of research toward developing novel multi-functional DNA-based hybrid materials.…”