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Utilising Size Selection to Enhance Gene Synthesis in Synthetic Biology Workflows

Biotechnology harnesses cellular and biomolecular processes to develop technologies and products. These products already improve our lives and show great potential for enhancing the health of our planet. In recent years and especially during the COVID-19 pandemic, the critical role of biotechnology and biomanufacturing in developing life-saving diagnostics, therapeutics and vaccines has been demonstrated and looks poised to progress on stratospheric trajectory, if we can successfully refine the technique to suit its myriad applications. Utilising a size selection technology which uses machine vision algorithms to monitor electric mobility and then respond in real time gives us the ability to enrich DNA through size selection with industry-leading precision.

Next-generation size selection instruments enable the dynamic target enrichment of DNA. The core automated size selection functionality is complemented by the ability to perform fragment length analysis and fluorescence assays for next-generation sequencing (NGS) quality control applications. For example, Yourgene Health’s Ranger® Technology offers a fast, effective and efficient automated solution for separating DNA molecules based on their size and electrical charge; it uses patent-protected, machine vision algorithms to interpret the gel electrophoresis process in real time.

Overcoming Challenges in Gene Synthesis

Gene synthesis forms the foundation of the new field of synthetic biology. It is also accelerating research in well-established fields by providing critical advantages over more laborious traditional molecular cloning techniques. De novo gene synthesis is required when template DNA molecules are not available, such as for codon-optimised sequences. It has been shown that synthetic modified viral sequences produce safer, more effective DNA vaccines. Codon optimisation can increase both the immunogenicity and the therapeutic anti-viral effects induced by DNA vaccines on various targets.

Some of the exciting areas are the clinical, pharmaceutical and other technology sectors struggling with sample purity. When considering the work done in these arenas, everything is highly dependent on the ability to manufacture new drug candidates in novel ways. This relies to an increasing extent on synthetic biology, which is an application that we have really good utility overlap with. Size selection is about enriching and purifying, in other words getting rid of the stuff that you don’t want and keeping the high value targets that you do want by differentiating based on size.

Gene synthesis can be challenging. Traditionally, we talk about a process that uses a lot of old bench techniques that have been around for decades. The process is predicated on synthesising a construct which is as pure as possible and then you’ve got to clone it. Of the many risks and difficulties associated with the process, this is the largest hurdle in a market which demands complex, quality DNA on increasingly tight turnaround times.

There are many stages in which impurities and error can be introduced early during the building of the construct, and several steps further down the line which jeopardise the chances of isolating your construct, not least when transforming it into a bacterial host. Then you have to let it grow for a while once it’s plated out, and finally begin the laborious task of sampling dozens of colonies before you find the exact construct of interest.