Lexicon Genetics Announces New Method For Creating Targeting Vectors

Lexicon Genetics (The Woodlands, TX) has developed a new approach to creating knockout vectors that could aid in the study of newly discovered human genes and in validating potential drug targets. As reported in the June issue of Biotechniques, Lambda KOS, the company's proprietary gene targeting and gene replacement system, combines the advantages of the lambda knockout vector (l KO) with the efficiency of yeast homologous recombination in its lambda knockout shuttle vector (l-KOS). This development significantly speeds up the process while allowing the creation of both simple and complex gene targeting vectors.

"Identifying valid drug targets is one of the critical issues in developing new therapeutics," said Arthur Sands, president and CEO of Lexicon Genetics. "The Lambda KOS system provides the flexibility to rapidly alter virtually any gene in any way to accelerate the drug discovery process, providing an important advantage in the race to understand the human genome."

Several companies and research groups have already registered successes with Lexicon's Lambda KOS system—among them Merck & Co., ZymoGenetics, Genetics Institute, Cephalon, H. Lundbeck A/S, The Rockefeller University, Tufts University, and University of Rochester, according to a company statement.

The Lambda KOS gene targeting and replacement system was developed by Michael Nehls, VP of genomics, and Sigrid Wattler, scientist, at Lexicon Genetics. Prior to development of this system, traditional methods could require several months of screening genomic libraries to complete the construction of some of the more complicated knockout vectors. Lexicon's approach converts a traditional lambda genomic library into high copy number plasmids (pKOS) using CRE-mediated recombination. This step, in addition, puts in place a positive/negative selection system that works in embryonic stem (ES) cells.

With the new Lambda KOS system, Lexicon can complete a gene targeting vector in less than three weeks, providing its collaborators a rapid route to drug discovery. Using the Cre/loxP recombinase system, which Lexicon has licensed from DuPont Pharmaceuticals, Lexicon can enhance the potential of the system by generating a variety of gene modifications on the vectors—point mutations, humanized alleles, and conditional mutations.

"Our novel high-throughput Lambda KOS vector system combines the advantages of several modern technologies such as PCR-based screening of arrayed genomic libraries, CRE/lox-mediated plasmid conversion, and restriction-independent target vector construction by yeast-mediated homologous recombination, as well as positive/negative selection in embryonic stem cells," said Nehls. "The Lambda KOS technology enables Lexicon to generate mice with predefined mutations at an unprecedented speed. In effect, we can go from library screen to ES cell electroporation in 3–4 weeks, at whatever level of mutation specification is desired."

Lexicon Genetics Inc. designs and developments high-throughput mutagenesis technologies for studying functional genomics in mammalian systems. Lexicon's Human Gene Trap Database and OmniBank library of gene-trapped mouse clones use bioinformatics software to compile and annotate both proprietary and publicly available genetic information to create an integrated functional genomics platform for use by pharmaceutical and biotechnology companies in drug discovery.

For more information: Lori K. Pinkerton, Marketing/Corporate Relations, Lexicon Genetics Inc., 4000 Research Forest Dr., The Woodlands, TX 77381-4287. Tel: 281-364-0100 or 800-578-1972. Fax: 281-364-0155.