Revolutionizing Biotechnology

By Joseph Jeong and Tony Chao
The Old English alphabet is generally regarded to have been invented around the 5th century. Literacy, however, at that time was mostly a privilege enjoyed by the upper elite class in the Western world. This all changed with the invention of the Gutenberg printing press around 1450, when literacy became democratized and available to laypeople. The printing press revolutionized the world, transitioning the end of the Dark Ages to the beginning of the Renaissance. Could we be witnessing a similar revolution in the biotechnology space? The Applied Ventures team thinks so, and recently expanded our portfolio with an investment in Twist Bioscience Corporation, an advanced biotechnology start-up based in San Francisco developing a proprietary semiconductor-based technology platform with the potential for synthetic gene manufacturing.

Last month Applied Ventures participated in a Series B financing round for Twist along with other strategic corporate and venture investors. The funds provided will be used to collaborate on platform development and enable next-generation silicon-based technologies with improved throughput, quality and cost. The investment also presents an opportunity to leverage Applied Materials’ expertise in precision materials engineering to add value to cutting-edge and potentially disruptive emerging growth opportunities in biotechnology, including applications for personalized medicine, sustainable chemical production, improved agriculture production, and new areas such as in vivo diagnostics, biodetection and data storage.

Essentially, Twist is attempting to build the biological equivalent of the Gutenberg printing press. Why is this important, you ask?

First, a brief history on DNA sequencing, or the reading of DNA. Though the double helix structure of DNA was first discovered in 1953, it was not until the 1970s that DNA could be sequenced and analyzed reliably. DNA sequencing technologies have improved rapidly since then, and today’s smartest minds are now socializing the idea of a $1,000 genome and sequencing DNA for entire populations of species. The below graph from the National Human Genome Research Institute (NHGRI) shows the magnitude of the sequencing cost-curve improvement relative to the semiconductor industry’s bread and butter, Moore’s Law:

Source: National Human Genome Research Institute

Through disruptive improvements in quality and cost, DNA sequencing is now enabling better insight of the biological world. Today for example, the healthcare industry is able to gain a deeper understanding of cancer, which is essentially a disease of the gene. Algae and bacteria are now being harvested to produce useful bio-products such as biofuels and neoprene.

But DNA sequencing alone is not responsible for all of these breakthroughs and applications. DNA synthesis is equally important.

Initial development on DNA synthesis began in the 1950s, even earlier than sequencing, and is somewhat ironically responsible for the dramatic improvement in DNA sequencing so many years later. Today’s sequencing methods essentially involve “sequencing-by-synthesis” which is the production of short single strands of DNA called oligonucleotides. However, the process is somewhat limited in its ability to improve over time, as seen by the below graph by Dr. Rob Carlson of Biodesic:

The reason DNA synthesis has not been able to keep up with improvements in sequencing throughput and parallelization is because of limitations with its semi-automated process, which traditionally requires human labor and significant amounts of expensive bio-reagents.

Twist’s innovative technology aims to change this paradigm by fully automating the synthesis process via a silicon-based manufacturing platform that will enable large-scale, high-throughput construction of genetic designs. All while overcoming industry inefficiencies by producing DNA on silicon instead of traditional plastic.

Imagine a world where DNA can be automatically printed like words on a document. That is the kind of world Twist is trying to create.

We are only beginning to tap into the potential of having the capability to both read and write DNA, and the applications are only limited by our imagination. Imagine tomorrow’s truly personalized healthcare system, where a patient sees a doctor for an ailment, and the patient’s DNA is sequenced with that of the bacteria or virus affecting them, to create a personalized medicine designed specifically for your DNA for maximum effectiveness. No more antibiotics, no more generic drugs, no more misdiagnosis; just a perfect understanding of your body and your ailment.

Twist’s CEO Emily Leproust, Ph.D, captures it best when she says: “We believe that Twist’s proprietary semiconductor-based DNA synthesis process using silicon as a platform will provide increased speed, quality and throughput, as well as reduced cost, to the design/build/test research cycle for developing better biologics, diagnostics, industrial chemicals and agbio products. Applied Ventures’ invesment bolsters our financial position and provides us a strategic partner with exceptional expertise in precision materials engineering to assist our aggressive development efforts to commercialize our first products in 2015.”

—Joseph Jeong is a senior investment associate for Applied Ventures, the venture capital arm of Applied Materials. Tony Chao is an associate investment manager at Applied Ventures.