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Life Tech Expands Synthetic Biology Portfolio with TAL Effector License

By Bernadette Toner

NEW YORK (GenomeWeb News) – Life Technologies said today that it has signed an exclusive license agreement for technology that enables synthetic biologists to selectively modify the gene expression of genetically engineered organisms.

The company licensed the methodology, called transcription activator-like effector technology, from its developers, a team of researchers at the Institute of Biology at Martin-Luther-Universität Halle-Wittenberg in Germany who first published the method in Science in 2009.

Life Tech has acquired a broad license to the TAL Effector technology, with the exception of commercial applications in plants. Those rights are exclusively held by the Two Blades Foundation, a nonprofit group that supports research on plant disease resistance. Life Tech retains the rights to plant research applications.

The TAL Effector technology allows for the design of proteins that bind to any specified sequence of DNA — an approach that promises precise functional control over genetic circuitry. The method enables targeted gene activation or repression; the addition, removal, or editing of genes; and site-specific gene insertion.

As described in the 2009 Science paper, the Martin-Luther-Universität Halle-Wittenberg researchers determined that repeat regions within TAL effectors are the key to their target specificity, with certain repeat types correlating with specific base pairs in the target DNA. The researchers demonstrated in that paper that they could generate artificial effectors with novel DNA binding specificities, which they experimentally confirmed in plant cells. In subsequent work, most recently in a paper published in PLoS One, the researchers showed that the approach can also be used to induce the expression of human genes.

The TAL effector technology is similar in some ways to zinc finger nuclease technology, which also relies on engineered DNA-binding proteins to enable targeted genome editing, but the researchers note in the PLoS One paper that compared to zinc finger proteins, "the DNA-binding specificities of TAL proteins are considerably easier to predict."

In another paper, published in Current Opinion in Microbiology in February, the researchers explain that the binding specificity of ZF proteins "is not completely predictable, because specificities of neighboring ZFs interdepend, which results in highly laborious screening of libraries to identify suitable candidates." TAL proteins have "an obvious advantage," they added, "because the TAL-DNA-binding specificity is unambiguously predictable and TAL repeat specificity is obviously neighbor-independent."

Life Tech believes the TAL Effector technology could be applicable in the healthcare, agriculture, and energy markets, with particular promise for bioproduction, stem cell research, vaccine development, and drug discovery.

Wendy Jozsi, director of synthetic biology at Life Tech, told GenomeWeb Daily News that the company found the technology "compelling" because it "broadly enables targeted genome engineering."

In healthcare applications, for example, she noted that many diseases are the result of over- or under-expression of a gene, so "targeted knockdown to certain areas of the genome based on the binding site specificity of TAL effectors" could eventually show promise in therapeutic applications.

Nathan Wood, vice president and general manager of synthetic biology at Life Tech, said the firm believes "there's no other technology on the market like it — specifically, how it works with the same specificity." He added that this provides scientists with "the ability to be more rational in their experimental design."

Life Tech stressed that it is still in the early stages of commercializing the TAL Effector technology and has not yet identified any specific application areas for it. The company initially plans to make the technology available as a custom service through GeneArt, the Regensburg, Germany-based gene synthesis subsidiary it acquired in December after acquiring a majority stake in the firm earlier in the year. Longer term, it also plans to introduce "off-the-shelf kits" incorporating the technology, Wood said.

The license agreement is in line with Life Tech's strategy to increase its footprint in the synthetic biology market — a sector that is estimated to reach up to $2.4 billion by 2013, according to a report by BCC Research.

The agreement "fits into our desire to build out the most complete synthetic biology toolbox," Wood told GWDN, adding that the company aims "to do for synthetic biology what the Life Tech and Invitrogen and ABI brands did for genomics."

Wood noted that the "first step" Life Tech took in this direction was its acquisition of GeneArt last year. "That was really along our strategy of being able to read DNA with our sequencing machines and also having the ability to write DNA with the GeneArt acquisition and brand," he said.

As it looks to further build out its synthetic biology portfolio, the company is keeping a lookout for "any tools that allow our research community and industrial customers to be able to go in and modify organisms for specific industrial processes," Wood said.