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Wyss Researchers Develop Low-Cost, Reliable, Rapid Gene-Synthesis Technology

Wyss researchers have developed a technology for synthesizing whole genes, and potentially whole gene circuits, that is faster, more accurate, and significantly less expensive than current methods. In this interview, Sriram Kosuri, discusses the technology and its potential. Learn more...

Next-Generation Tool Could Overcome Critical Research Obstacles; Lead to Creation of New Engineered Organisms for Medicine and Energy

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have developed a technology for synthesizing whole genes, and potentially whole gene circuits, that is faster, more accurate, and significantly less expensive than current methods.

Synthesis of single large DNAs encoding entire genes offers the promise of designing and building complex gene networks with desired functionalities from the ground up. Using this technology, cells and organisms could be engineered to have novel and complex capabilities, such as producing vaccines and drugs, regenerating injured tissues, or cleaning up pollution. But the lack of effective and economical tools for creating the long stretches of DNA required to reengineer living cells has been a huge obstacle to achieving these goals.

These longer, gene-sized fragments are currently created in a costly and time-consuming manner by stitching together short strings of nucleic acids known as oligonucleotides. Where the bottleneck occurs -- and where the expense mounts -- is in the production of these smaller building blocks, which are most often synthesized just one at a time.

Recent technological advances have made it possible to create hundreds of thousands of these oligonucleotides on a single DNA microchip.  However, synthesizing whole genes from this mixture has been problematic because of the difficulties in separating the handful of oligonucleotides needed to make a specific gene from the vast numbers that could be used to make other genes.

Sriram Kosuri and Nikolai Eroshenko, working in the Wyss Institute's Biomaterials Evolution Platform, which is led by George Church, Ph.D., a Wyss core faculty member and Professor of Genetics at Harvard Medical School, addressed this challenge. The team developed a new method that reduces the complexity of these mixtures by amplifying individual subpools using a series of selective enrichments. 

Their technology provides a reliable and scalable method of synthesizing genes from DNA microchips.  It also offers a ten-fold reduction in cost over existing methods, paving the way for significantly expanded commercial and research applications in the future.

"We're very proud of this work, which represents a major breakthrough in gene synthesis technology development and has the potential to transform the fields of Synthetic Biology and Genetic Engineering," said Wyss Institute Founding Director, Donald E. Ingber, M.D., Ph.D. "This innovative new solution could bring us several steps closer to realizing the full potential of Synthetic Biology to address real-world medical needs and real-world environmental issues."

The Wyss Institute is the leading entity focused on the emerging field of biologically inspired engineering in which researchers explore the design principles used in nature and apply these insights to engineer new materials and devices for medicine, industry, and the environment.  The Institute operates as an alliance among premier academic and clinical institutions in the Greater Boston area, bringing together world-renowned scientists and engineers.

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