Fikri Alemdaroglu and Andreas Herrmann, scientists at the Max Planck Institute for Polymer Research, Mainz, Germany, are making the most of  a new class of bioorganic hybrid materials

There has been significant and rapid progress in polymer chemistry and molecular biology in the past few decades. Macromolecules can now be prepared with predetermined molecular weights and reasonable structural control, thanks to advances in a variety of polymerisation techniques. And the development of automated synthesis of DNA has made this biopolymer much more widely available than ever before. 

Recently, polymer chemistry and molecular biology have converged to create a new type of hybrid material, made of oligodeoxynucleotides (fragments of DNA) and organic polymers. By combining these two materials, DNA block copolymers are generated, which have properties that cannot be realised using polymers or nucleic acids alone. 

These bioorganic hybrids can be made by coupling a DNA fragment and a synthetic organic polymer in solution or on a solid support. This offers the option of varying the nature of the synthetic polymer, and the length and sequence of the oligodeoxynucleotide. This straightforward tailoring means DNA block copolymers have quickly found application in the fields of DNA detection, gene therapy and nanoscience. 

Amphiphilic hybrids, which have a hydrophobic and a hydrophilic part, can self-organise on the nanoscale. In water, amphiphilic DNA block copolymers aggregate to form micelles with a hydrophilic DNA shell and a hydrophobic polymer core.  The amphiphilic copolymer of DNA with poly(lactic-co-glycolic acid)  has been used to deliver antisense oligodeoxynucleotides, which are complementary strands of DNA that can bind to target DNA, switching off the function of particular genes. The cellular uptake of the DNA fragments, and the reduction in gene activity were both found to be greatly enhanced when using the DNA block copolymer compared to DNA alone.

The hydrophobic part of the DNA-poly(lactic-co-glycolic acid) block copolymer softens at a very high temperature, making it difficult to dissolve and so hindering the investigation of the micelles' properties. But using a polymer like polypropylene oxide (PPO), which has a low softening temperature, as the hydrophobic block, allows the micelles to be prepared simply by dissolving the hybrid polymer in water. And what's more, PPO has proven to be biocompatible with different cell types, which is clearly important for use in living systems.
  
DNA-PPO copolymers form spherical micelles that have been used as scaffolds for DNA-templated organic reactions.  Complementary DNA strands equipped with reactants can be clicked in to the outer shell of the micelle, which is made of single stranded DNA fragments. Chemical transformations, such as peptide bond formation, are accelerated, because the reactants are held in close proximity. 

In the field of nanoscience, it is still a challenge to precisely control the size and shape of self-assembled aggregates. The self-recognition properties of the nucleic acid segments in DNA block coplymers can be exploited to this end. The shape of DNA-PPO micelles can be transformed from spheres to rods, with precise control over the length of the nanorods, by hybridizing the DNA fragments with their complementary strands.

Undoubtedly, connecting synthetic polymers with DNA fragments leads to materials with properties which could not otherwise be achieved. Since the synthetic routes are well established, it is now time for chemists, material scientists and biologists to start focusing on the applications of these bioorganic hybrids, allowing them to fulfill their potential.

Read Andreas Herrmann's Emerging Area article on 'DNA meets synthetic polymers-highly versatile hybrid materials' in a forthcoming issue of Organic & Biomolecular Chemistry.