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Genomics in San Diego: From the Human Genome to a New Biotechnology Focus

Xconomy San Diego — 

San Diego’s biotechnology industry has played an integral part in advances in genomics. Our reach extends from the research and tools created by startups during the genomics boom that began in the late 1990s, to cost-saving improvements made in DNA sequencing and the new field of synthetic genomics, which may provide important advances from biofuels to personal health. Looking at the history of local companies that helped shape the genomics industry gives us insights to the future, a topic we will also be discussing at the San Diego Biotechnology Network’s 10th Anniversary of the Human Genome event on August 18th. The evening will feature experts from Illumina, Synthetic Genomics, UCSD, the Genomics Institute of the Novartis Research Foundation, Fate Therapeutics, and Accelrys.

We’ve created a list of genomics companies in San Diego, with the companies listed according to the date they were founded or their first landmark in genomics. After the first announcement that the human genome had been sequenced in 2000, many thought that a “gold mine” of new disease targets awaited, and early efforts focused on identifying protein structures and functions. Companies forming in this era include GeneFormatics, ActivX, and Structural Bioinformatics. However, we soon realized that this was not enough; that drug targets must be validated by biology in order to “mine” them. In those early years, I was part of a genomics startup in San Diego called GeneFormatics, and we did some very interesting work with protein structure predictions. But like many other investigators, I think we might have lacked the crucial “gene to disease” piece required to use genomic data to create drugs. Even Craig Venter has said, “we have learned nothing from the (human) genome,” meaning that the realities of learning about health and disease are more complex than just understanding our genetic code.

Structural biology has always been a strong suit in San Diego, fueled by The Scripps Research Institute (TSRI) work on behalf of the Protein Structure Initiative and the San Diego Supercomputer Center at UC San Diego, which helps maintain the Protein Data Bank. High throughput protein structure companies Syrrx and Structural Genomics came on the scene in the late ’90s, along with the Genomics Institute of the Novartis Foundation (GNF) which is arguably the first translational research organization in San Diego.

The establishment of GNF, which brought big pharma literally to TSRI’s front yard, fueled another driving force in San Diego, known as “high throughput genomics.” The development of sophisticated robotics helped GNF, Syrrx, SGX Pharmaceuticals, and Kalypsys to push the boundaries of automating high throughput structural determination and screening. Indeed, GNF and Kalypsys both have developed robotics products for drug discovery. These advances can certainly be considered part of San Diego’s contribution to the genomics field, and helped pave the way in drug discovery.

Some might say the utilization of genomics for drug discovery also has come full circle in San Diego with Fate Therapeutics. They have developed a novel platform that utilizes high throughput gene expression data analysis in combination with small molecule screening in stem cells and derived cell types to find new therapeutics. Stem cells represent an ideal way to create and screen rare cell types, and of course Fate represents one of the most promising areas of biotech research today.

San Diego drug discovery companies also have utilized genomic information to focus on protein families, with Ambit Biosciences using competition binding assays to drive their own kinase drug discovery research, as well as providing the related KinomeScan product as a research tool. ActivX’s technology, which came from TSRI, focuses on gaining information from enzyme family active sites through covalent modification. Phenomix, a GNF spinoff, took a different tactic to simplify the gene-to-disease problem, first by screening physiological models, and then identifying the genes responsible. All three companies are still in existence, relying on partnerships, products, or services to stay afloat and to put compounds to the clinic. But none has reached the market yet.

Even before the completion of the human genome project, San Diego companies were developing important tools for analyzing genomic DNA. Sequenom, founded in 1994, is perhaps the first of these DNA-focused companies. Sequenom’s mass spectrometry-based DNA analysis tools are used by researchers to find single nucleotide polymorphism (SNP) and methylation sites, and the technology also is used for prenatal diagnostic tests.

Illumina is considered by many to be San Diego’s genomics “rock star.” It was founded in 1998, after licensing “BeadArray” technology from Tufts University, which facilitated larger scale and multiplex genome sequencing efforts. In 2006, Illumina acquired Solexa, bolstering their array products with whole genome sequencing technology. Their announcement offering personal human genome sequencing for less than $50K earlier this year shows their dedication in moving into the direct-to-consumer (DTC) genomics market.

I worked in a small informatics group in the early part of this decade at what’s now known as Life Technologies in Carlsbad, CA, and experienced the first “genomics wave” creating early web 2.0 tools. At that time, Invitrogen was known as a clear leader in molecular biology research tools, but the 2008 merger with Applied Biosystems (ABI) (the combined companies became Life Technologies), secured their place in the genomics hall of fame. ABI instruments were the workhorses of the human genome project, and Life Technologies continues to move strategically toward more patient-focused markets. Life’s acquisition of molecular diagnostics company Acrometrix, their relationship with Tgen, and the creation of the Genomic Care Alliance all point in this direction.

Does Life Technologies’ investment in Synthetic Genomics (SGI) fit this trend? Hard to say. Life CEO Greg Lucier hinted that the company plans to collaborate with SGI on research tools when he said, “Life Technologies … will be able to directly participate and lead in synthetic biology by offering the tools our customers need to accelerate discoveries in this emerging field.” But it’s hard to believe that Craig Venter and Greg Lucier don’t have bigger designs for using synthetic genomics to improve human health.

Of course, the genesis and inspiration for most of the companies that have influenced genomic progress in San Diego can be found at our outstanding universities and institutions. Technology and people from TSRI, UCSD, the Sanford-Burnham Medical Research Institute, and others have all contributed greatly to the success of the companies in the region. These institutions also contribute by establishing translational research centers such as the Sanford Burnham Molecular Libraries Probe Production Centers Network (MLPCN), the Scripps Translational Science Institute, and the UCSD Clinical and Translational Research Institute.

While sitting at Xconomy’s San Diego Life Sciences 2030 event earlier this year I felt as though a time machine had transported me back ten years. The panel indicated that one of the next big opportunities for our local industry would be bioinformatics startups. This sentiment partly fueled the biotech startup boom in the early 2000s. While great tools and advances resulted, I wouldn’t say many would consider it a big economic success for our region. Will this round of analyses prove more fruitful for human health, or are we back to the drawing board, with the only difference being that we have more data now? The fact that our local industry has found ways to reduce the complexity of the human genome, whether by enzyme family, single cell analysis, or by reconstructing life, bodes well for the region.

Editor’s note: Mary Canady has worked for Life Technologies, Accelrys and Sequenom, and has had business relationships with Fate Therapeutics and Illumina through the San Diego Biotechnology Network (SDBN). She was not compensated by these companies for this article, but received sponsorship fees from Accelrys and Illumina for next week’s SDBN event.