Open Competition 3 - Biotechnology (September 2002)

Targeted Activation of Multiple Genes in Plants Using a Single Engineered Transcription Factor

Sponsor: Sangamo BioSciences

• Project duration: 5/1/2004 - 4/30/2007
• Total project (est.): $2,822,639.00
• Requested ATP funds: $1,987,774.00

Genetic engineering in plants typically involves the introduction of a gene that directs production of a specific protein or enzyme. This approach of over-expressing one molecule is typically met by bottlenecks elsewhere in a synthetic pathway, thus limiting the potential to increase levels of multiple valuable products. Moreover, separately inserting and activating several different genes in one plant to control its metabolism is technically difficult and currently impractical. To address this problem, Sangamo BioSciences plans a three-year project to develop and test technology to genetically engineer plants by introducing a single transgene for a novel protein switch capable of activating mutiple genes involved in biosynthesis of commercially important products. The company already has developed novel "protein molecular switches," or zinc finger DNA-binding protein transcription factors (ZFP-TF) that can bind selectively to target DNA sequences and turn important genes on or off. The project will design multiunit ZPF-TFs that can bind to and regulate several genes in a biochemical pathway, enabling activation of sets of up to eight genes. Sangamo plans to identify individual ZFP-TFs for making Vitamin E and develop a multiunit ZFP-TF transgene for regulating the synthesis of this vitamin in Arabidopsis. Technical challenges include the possible presence of more than one DNA target sequence for the same multi ZFP-TF protein, possible binding to inappropriate gene promoters, and achieving uniform switch activity. The project would not proceed without ATP funding because the technical risk is too high for private investors. The new technology is envisioned as being broadly applicable to enhancing virtually any multigene trait in any organism. For instance, it could be used to increase the vitamin E content in soybean seed and at least triple soybean vitamin E production, enabling the United States to capture the world market for this vitamin. The technology has the potential to increase either crop yield or revenue by at least 10 percent annually, equivalent to $5 billion to $7.5 billion. The use of commercial crops to produce pharmaceuticals, vaccines, industrial chemicals, and other products could reduce dependence on petroleum. The global market for bioengineered crops exceeds $100 billion annually. Multiunit ZFs also have potential applications in gene targeting and gene therapy.

For project information:

Dr. Casey C. Case, (510) 970-6000 x202
ccase@sangamo.com

ATP Project Manager

Michael Amos, (301) 975-8631
michael.amos@nist.gov