TUNABLE GENEREASSEMBLY™ (TGR™) TECHNOLOGY

Reassembling the Best Properties of Different Genes

Verenium uses Tunable GeneReassembly™ technology to optimize the characteristics of proteins by combining their best properties into a new, high-performance molecule. This next-generation technology significantly expands the genetic diversity available to be screened by creating populations of DNA segments of various lengths and then reassembling them to generate new genetic variants. This significantly increases the probability of finding gene products that will lead to novel and next-generation enzymes and biopharmaceuticals.

TGR™ can be used to evolve properties encoded by single genes, multiple genes, or entire genomes. The TGR™ approach, unlike traditional DNA shuffling technologies, allows related as well as unrelated genes to be combined to maximize evolved improvements. In contrast to random PCR shuffling, TGR™ technology is tunable, which means the process can be sensitized to the needs specific for targeted enzymes and protein biopharmaceuticals.

The TGR™ Process

1. Identify Parental DNA
2. Engage Bioinformatics

By screening the genes or proteins derived from environmental gene libraries for desired characteristics, Verenium identifies the parental DNA to be reassembled into new gene variants. Alternatively, our partners can define the parental DNA for any given gene evolution project.

The sequences of the parental DNA are transferred into powerful computer programs. We define the conditions under which gene evolution will be implemented; these conditions can range from complete randomization to fully defined combinations.

3. Produce Chimeric Variants
4. Express and Screen Variants

The result is a population of chimeric gene variants whose number depends on the number of programmed variants. This population can be relatively simple as, in the case of mutant combinations, to extremely complex, as in the case of pathway or genome evolution.

This population is recloned into a suitable expression system and screened for improved performance. The screening process is project specific and can include in vitro and/or in vivo systems.

5. Select Optimal Variant(s)
6. Generate Optimized Protein

Through this effort, Verenium identifies the variant or variants that meet all design standards.

The newly optimized protein exhibits the best attributes of its parental genes for the relevant application.