When we think of synthetic biology we think of the power of genetic engineering; moving genes between organisms, modifying the coding for a protein to improve its efficiency, incorporating a metabolic pathway or two to perfect our microbial factory. But what we often forget is that the most cleverly designed gene is useless if it isn’t transcribed and translated to make our protein of interest. This process is just as important in developing a bioproduction strain, and the effective design of a gene promotor (those oh-so-underrated pieces of DNA) can be the difference between industrial-scale yields and a yeasty stew.
Focusing on this side of the equation is Synpromics, an Edinburgh-based company with a goal to develop improved, synthetic promoters.
Their core technology is an algorithmic approach which identifies the ‘gene expression profile’ of a wide range of cellular tissues and conditions – e.g. which genes are currently being activated in corn leaves 3 weeks after sprouting? Using this knowledge they can design promoters which are only active under this set condition, allowing one to target the genetic modification extremely precisely.
With a wide range of sources to draw from, Synpromics has begun development on promoters for systems ranging from crops to bacteria, yeast to CHO cells. Having said this, their work is fairly evenly split between promoters for agroscience and pharmaceutical industries, in particular gene therapy for visual disorders.
Synpromics is a relatively young company, having been founded in 2010 as a spin-off to commercialise technology developed by Dr. Michael Roberts (who currently acts as CSO to the company). The company has secured funding from the Scottish Investment Bank (the investment arm of government technology development group Scottish Enterprise), raising GBP 250,000, after which further rounds of investment pulled in GBP 2.1 million from Calculus Capital, a UK-based VC/private equity group.
These investments are a sign of faith in Synpromics, a faith which appears to have been justified by some of their announced research collaborations and contracts. The company is partnered with Dow Agroscience for the development of crop synthetic promoters, while beyond this Synpromics is heavily involved in the development of gene therapy treatments for rare eye diseases. As part of this they have collaborations in this direction with Avalanche Biotechnologies, Applied Genetic Technologies Corp (a gene therapy biotech with the highly appropriate stock ticker AGTC), alongside other therapeutic targets including liver disease.
A number of companies in the synthetic biology sphere have come slightly adrift with recent decisions in America and Australia preventing the patenting of naturally derived DNA sequences. Synpromics avoids a number of these problems by following a patenting strategy that protects their design algorithms, rather than the sequences themselves. Having said that, as fully synthetic constructs the promoters are likely all of the problems that companies such as Myriad Genetics have had.
Several of Synpromics’ collaborations cover ‘gene therapy’, the use of adeno-associated viruses to deliver replacement genetic material to patients. Control of gene expression and immunogenicity is extremely important for this process (immunogenic reactions in particular being responsible for an early gene-therapy death). The 15 years since this incident, however, have led to a large increase in the number and safety of gene therapy clinical trials – making it the perfect example of a growing field. The expansion of genetic therapeutics, coupled to the strong growth in genetically modified crops, ensures that Synpromics’ future is looking brighter by the day.
For proof of this, look no further than the collaboration between Synpromics and Cell Therapy Catapult which was announced today. Cell Therapy Catapult is a centre for cell and gene therapy research and commercialisation, with over 100 employees helping to move new technologies into clinical trials and beyond. This joint venture will cover the development of new biofactories, cell lines which are capable of producing large amounts of viral vector for use in gene therapy. Spanning three years and covered partly by a GBP 2 million grant from Innovate UK, the end goal will be several cell lines with inducible, high viral-titre production capabilities. This will represent a significant improvement over current methods, which require laborious and slow techniques to develop ineffective, low-yielding lines, and may open up gene therapy to a number of diseases which have so far proved untenable to treat.
In a press release, Dr. David Venables, CEO of Synpromics, expressed his enthusiasm:
This will be the fifth major collaboration for Synpromics to apply our synthetic promoters in gene therapy. We believe Synpromics’ technology will provide a critically needed solution to high titre, industrial scale, vector manufacture, a critical barrier in the gene therapy industry. The result of this solution will be a major advance to the commercialisation of gene therapies in non-orphan drug indications.
Come along to the upcoming SynBioBeta London 2016 conference to hear a bit more about their plans for the future.