Courtesy of Invitrogen
Scientists studying a protein's function frequently start with the gene that encodes it. "You want to know what a protein does at the biochemical, cellular, physiological, and organismal levels," says Marc Vidal, assistant professor of genetics at Harvard University and research associate at the Dana-Farber Cancer Institute. "To do that, you need to express this protein under many different conditions using the region of the gene that encodes it, and that's the open reading frame--the ORF." With two new programs from Carlsbad, Calif.-based Invitrogen, researchers can now purchase ORF clones.
Invitrogen's Ultimate™ ORF Clone Collection consists of about 4,400 human and 2,800 mouse ORF clones, and climbing. "We are constantly expanding this collection," says Tanya Boyaniwsky, manager for Invitrogen's clone collections. Eventually, the company hopes to offer ORF clones for every human gene, plus all single nucleotide polymorphisms (SNPs) and splice variants.
To keep track of all this information, Invitrogen developed an online search and ordering tool called the Ultimate ORF Browser. Information is arranged according to the Gene Ontology (GO), a vocabulary that is used to annotate eukaryotic genes. The GO vocabulary starts with terms structured into three broad categories that reflect the biological roles of genes: molecular function, biological processes, and cellular components. "Out of the term molecular function, you can choose enzyme," Boyaniwsky explains. "Out of enzyme, you can choose many different kinases. Once you find your specific term or gene name, you simply click the link provided to access available ORF clones." Users also can search for an ORF clone by keyword and other descriptors.
Invitrogen also has simplified the transfer of genes to different vector systems for scientists asking multiple questions about a single protein. In the past, this process required cloning, subcloning, and validation each time the clone went into a new system. To overcome this problem, Invitrogen makes its ORF clones with its own Gateway® Technology, a recombinase-based system that enables the rapid transfer of a single gene into many different vectors.
PRICED TO MOVE Invitrogen has priced its ORF clones in an academia-friendly manner. Vidal points out that some labs work with several hundred ORFs simultaneously, and a high price tag could make these researchers shy away from commercially prepared clones. "It's probably worth it to pay $1,000 for one ORF so that my postdoc doesn't have to go back and clone it. But, in my lab, when we work with 5,000 ORFs at a time, I need a better price," says Vidal.
For just one ORF clone, Invitrogen charges what Vidal is willing to pay--about $1,000 for academics, with volume discounts for multiple clones. For biotechnology companies or large pharmaceutical companies, Invitrogen created its ORFeome BioCharter™ Program. To join, a company pays membership fee, which entitles it to discounted prices on ORF clones, input on which ORF clones get developed in the future, onsite research and development support, and more. "We have different pricing for academic, biotech, and large pharma," says Siamak Baharloo, marketing manager for BioCharter. "It really depends on the extent of the involvement that they want." Invitrogen encourages academic labs to form groups to join this program, in order to reduce costs.
Still, scientists worry about more than affordability. Some, for example, are concerned that the use of commercial ORFs may limit future intellectual property protection. "If you receive 300 ORFs and you introduce them into 10 different vectors, you now have 3,000 pieces of resources. You want to make sure that your intellectual property is fine, that you're not going to be sued by someone for some bizarre reason," says Vidal. Invitrogen, though, leaves that responsibility to the user. Boyaniwsky says, "Once a customer focuses on a certain protein, and [begins to develop] a drug, I think that's the point where they're going to investigate intellectual property."
Boyaniwsky points out that Invitrogen provides a rare guarantee: that the amino acid sequences in the clones match what is in the public database. And, Invitrogen puts no limits on what a buyer does with a purchased ORF clone. As a result, Invitrogen's initiatives on ORF clones could hasten basic research and drug development.