Packaging DNA Origami into Viral Protein Cages

Abstract

The DNA origami technique is a widely used method to create customized, complex, spatially well-defined two-dimensional (2D) and three-dimensional (3D) DNA nanostructures. These structures have huge potential to serve as smart drug-delivery vehicles and molecular devices in various nanomedical and biotechnological applications. However, so far only little is known about the behavior of these novel structures in living organisms or in cell culture/tissue models. Moreover, enhancing pharmacokinetic bioavailability and transfection properties of such structures still remains a challenge. One intriguing approach to overcome these issues is to coat DNA origami nanostructures with proteins or lipid membranes. Here, we show how cowpea chlorotic mottle virus (CCMV) capsid proteins (CPs) can be used for coating DNA origami nanostructures. We present a method for disassembling native CCMV particles and isolating the pure CP dimers, which can further bind and encapsulate a rectangular DNA origami shape. Owing to the highly programmable nature of DNA origami, packaging of DNA nanostructures into viral protein cages could find imminent uses in enhanced targeting and cellular delivery of various active nano-objects, such as enzymes and drug molecules.

An Effective Multi-Stage Liposomal DNA Origami Nanosystem for In Vivo Cancer Therapy

“…In particular, DNA nanovehicles, once in the blood stream, are rapidly recognized by circulating DNAses and by the immune system, inducing inflammatory responses. The possibility to encapsulate DNA nanostructures in double-layer membranes or in a protein coating could avoid DNAse degradation and immune system activation, improving pharmacokinetics, bioavailability and biodistribution [10][11][12].Among the clinical-grade nanoparticle-based technologies, liposomal technology has become a very successful and rapidly developing area of preclinical and clinical research. With the advantages of biocompatibility, biodegradability, low toxicity, and aptitude to trap both hydrophilic and lipophilic drugs [13] as well as a desirable accumulation in tumor tissues [14], liposomes are very attractive and have been extensively investigated as a DDS.…”

“…In particular, DNA nanovehicles, once in the blood stream, are rapidly recognized by circulating DNAses and by the immune system, inducing inflammatory responses. The possibility to encapsulate DNA nanostructures in double-layer membranes or in a protein coating could avoid DNAse degradation and immune system activation, improving pharmacokinetics, bioavailability and biodistribution [10][11][12].…”