Solexa: second-gen genetic sequencing

The challenge for scientists seeking cures for diseases is the sheer scale and complexity of the human genome: around 3 billion base pairs long. Variations in this code have an immeasurable influence on an individual’s health. The goal was and is to apply innovative technologies and revolutionary assays to the analysis of genetic variation and function, making studies possible that were unimaginable just a few years ago. To that end, a DNA sequencing approach, developed by Solexa, has today made routine human genome sequencing a reality and accelerated the development of genomic personalised medicine.

How it all began: In the mid-1990s, Cambridge Professors Shankar Balasubramanian and David Klenerman were watching one of nature’s machines called a polymerase synthesise DNA.

A series of creative discussions in 1997 sparked ideas surrounding tracking the movement of DNA polymerase, by visualising single molecules as they incorporated nucleotides step-by-step on a solid surface. This technique, subsequently referred to as ‘sequencing by synthesis technology,’ or SBS, eventually became the basis of a new DNA sequencing approach.

In 1997, the pair met with Abingworth (Cambridge venture capitalists) with an idea that they said could improve the speed and cost of decoding DNA by a factor of 100,000-fold. In 1998, Balasubramanian obtained initial seed funding from both Abingworth (£600k) and Cambridge Enterprise to form Solexa. Early research and development work was conducted in the Cambridge Chemistry Department until 2000, when Solexa’s corporate facilities were established on the south side of Cambridge following a further £3 million investment from Abingworth.

In 2001, the team’s research progress attracted £12 million in Series A funding, enabling it to build its management team. Three years later, Solexa acquired Manteia’s molecular clustering technology. The amplification of single DNA molecules into clusters enhanced the fidelity and accuracy of gene sequencing, while reducing the cost of the system optics through generation of a stronger signal.

In 2005, the team sequenced the complete genome of bacteriophage phiX-174, the same genome the Wellcome Trust Sanger Institute first sequenced using his method. However, the SBS technology generated significantly more sequence data, delivering over 3 million bases from a single run.

Also that year, Solexa became an international public company (NASDAQ) with offices in Cambridge and California, and very quickly became a $200-million company. The first Solexa sequencer, the Genome Analyzer, was launched in 2006 and gave scientists the power to sequence 1 gigabase (Gb) of data in a single run. This 1G sequencer could sequence a personal genome for about $100,000 in three months.

Solexa and its technology were acquired by Illumina in early 2007 for $650 million. Since that time Balasubramanian has remained a senior advisor to Illumina and in 2015 the technology can sequence a human genome for just $1,000 in about a day – a million-fold improvement on the state-of-the-art at the start of the project in 1997. Today it is being used for population scale human genome sequencing as well as large-scale clinical sequencing, such as the NHS 100,000 Genomes Project, and is the global market leader in the field with about 80 percent market share.

You can learn more about Solexa in our film.

Tags: , , , , , , , , ,