STUART CROSBY
Evonetix Ltd, Cambridge, United Kingdom

Abstract

DNA synthesis is an essential part of synthetic biology, providing access to custom-made oligonucleotides (oligos) and double-stranded DNA, offering the potential to design new genes from scratch for an exciting range of applications, including pharmaceuticals, renewable energy and data storage. Synthesis usually proceeds via sequential chemical addition of nucleotide bases to a growing strand on a solid-phase support, before cleavage and hybridisation to generate double-stranded DNA. These methods are invaluable in research but become increasingly time-consuming and error prone as more bases are added.

The anticipation of a synthetic biology revolution has created huge demand for high-quality oligonucleotides and double-stranded DNA, resulting in several companies developing novel approaches to DNA synthesis. This article will outline the fundamentals behind DNA synthesis, including some recent advances in the field which have sought to overcome caveats by reducing synthesis costs and increasing sequence fidelity. In addition to this there will be some discussion of the potential for DNA synthesis to deliver solutions to current global challenges.

INTRODUCTION

Synthetic Biology

Synthetic biology is a term used to describe an approach by which novel artificial biological pathways, organisms or devices are designed and constructed (1). Today, many would argue that synthetic biology is at the cusp of enabling a multitude of major breakthroughs in the production of, for example, renewable chemicals, biofuels, pharmaceuticals and food ingredients. Already synthetic biology is positively impacting many of our present and future needs in medicine including the development of novel vaccines (e.g. antigen genes or nucleic acid vaccines), gene therapy (with its requirement for synthetic DNA), CRISPR-Cas9, and other cellular engineering techniques. For example, the field of immuno-oncology has yielded chimeric antigen receptor technology (CAR-T), a cancer cell therapy which engineers a patient’s own immune cells (T-cells) to recognise and attack cancer cells and this approach has already shown significant benefits for certain patients (2).

Synthetic biology is enabled by the vast amounts of DNA sequence information available from a ...