Fortuitous First Customer
The linker was developed in collaboration with Ribozyme Pharmaceuticals (now Sirna Therapeutics; www.sirna.com). The technology is exclusively licensed to Prime Synthesis. Starting in 1999, Sirna Therapeutics worked closely with Prime Synthesis to further develop CPG for the synthesis of larger quantities of RNA oligonucleotides for clinical trials.
The collaboration with Ribozyme also helped Prime Synthesis to establish a GMP-manufacturing facility to meet the needs of the pharma industry. The company recently completed construction of a 20,000-sq-ft GMP-compliant production area with a suite of organic synthesis work areas and state-of-the-art quality control laboratory.
Because of its early collaborations, Prime Synthesis focused on the large-scale therapeutic oligonucleotide market. Nearly every CRO that makes oligonucleotides uses Prime Synthesis CPG for some clients, according to Rothstein. The company is known for customized CPGs that produce the best results for a particular product, synthesis equipment design, and pricing objective, he says. For instance, a collaboration with Avecia Biotechnology (www.avecia.com) led to a chemical refinement that reduced the amount of an impurity and greatly lowered purification costs of the final product.
Prime Synthesis’ linker was developed to synthesize RNA-based oligonucleotides. As a result of recent advances in RNA interference, RNA-based drug development is becoming more popular.
RNA-based oligonucleotides, however, are more difficult to synthesize, but "this linker is exceptionally well suited for RNA synthesis," says Rothstein.
"The RNA area is starting to boom," says Fran Wincott, Ph.D., a synthetic organic chemist and consultant who advises companies developing RNA oligonucleotides. She recommends that her clients work with Prime Synthesis because of its track record. "Quality assurance people like Prime Synthesis," says Dr. Wincott.
Despite the advantages of glass for oligonucleotide synthesis, some researchers prefer polystyrene as a solid support, even though polystyrene may swell when exposed to solvents. Increasing the amount of cross-linking reduces swelling, but at the expense of nucleotide loading. Prime Synthesis responded to this market preference by introducing a new line of Prime Performance Polystyrene supports in 2006. "We developed one that has the best chance of success in the therapeutic oligonucleotide area," says Rothstein.
For more than a decade, many attempts have been made to create a universal support that does not contain one of four specific bases to initiate synthesis. Although there have been some successes, universal linkers give lower yields of fully cleaved and dephosphorylated oligonucleotides than do dedicated nucleoside supports.
Recently, a group at the University of Kuopio in Finland developed a universal linker that gives nearly 100% yield. "It uses a neutral functional chemistry that eliminates the need for base-specific supports," says Rothstein. Prime Performance offers the universal linker on both its CPG and polystyrene product lines, under license from Metkinen (www.metkinen.com) and Glen Research (www.glenres.com). A universal linker simplifies inventory and forecasting needs. "You only need one product instead of many," says Rothstein.
Prime Synthesis also launched a new division called 3-Prime (www.3prime.com) to make it easier for research customers to buy small quantities of its products online.