Dyax, Genetics Institute, Will Discover Novel Purification Tools
Dyax Corp. and Genetics Institute Inc. will collaborate on the discovery and development of novel affinity ligands for purifying one of Genetics Institute's biotherapeutic drug candidates. As part of the deal, Dyax will create small, chemically synthesizable affinity ligands using its proprietary phage display technology. These ligands will then be used to purify Genetics' protein. Both companies hope the artificial ligands will eliminate the need for generating animal-based affinity ligands in the purification.
Phage display is a novel way to express large libraries of peptides and proteins on the surfaces of phages — viruses that infect bacteria. In phage display populations of phages are combined with DNA sequences encoding for libraries of peptides or proteins. The phages then express these novel sequences, fused with their surface proteins, while the genes coding for that sequence reside within the phage.
Phage display creates a physical linkage between vast libraries of random peptide sequences and the DNA encoding each sequence, allowing rapid identification of peptide ligands for a variety of target molecules (antibodies, enzymes, cell-surface receptors, etc.). The in vitro selection process is known as biopanning (see figure).
Phage display produces what amounts to living protein/peptide libraries. Most peptide-displaying phages ignore the target molecule, but some bind to it. The ones that bind most strongly are the best affinity ligands. So what begins as a random assembly of peptides winds up, after binding and selection, as one or several highly specific ligands for the target. Ligands are covalently bound to chromatography media through a proprietary process and used to purify batches of protein.
To manufacture these ligands in useful quantities, the phages which have bound are identified and their genes are deciphered. Once this sequence is known the affinity ligand may be manufactured either by chemical synthesis (in the case of smaller peptides) or through recombinant expression in a suitable host organism.
Phage display cuts the time and cost of developing affinity ligands from scratch, a process that typically involves injecting animals with the target molecule, then harvesting the antibody either for direct use or for analysis and subsequent expression in microorganisms. In some cases the portion of the antibody responsible for binding is identified and this subset of the intact antibody is what is used.
For more information contact Susan Jones, vice president of technology, Dyax Corp., 1 Kendall Square, Bldg. 600, Cambridge, MA 02139. Tel: 617-225-2500, ext. 243.
By Angelo DePalma