HAMBURG, Germany - The Munich-based combinatorial biology company MorphoSys AG disclosed the development of the first method for the high-throughput generation of antibodies against protein fragments derived from expressed sequence tags, or ESTs.
The technology could significantly speed up the functional analysis of the human genome.
In the search for new genes distributed along the human genome, two different approaches are being pursued. One method uses bioinformatics software to identify open reading frames in the sequence of large cDNA fragments that have been isolated and cloned from genomic DNA. This procedure is tedious as it requires extensive, costly sequencing work and sophisticated software solutions.
In an alternative, short-cut approach, cDNA is synthesized using mRNA as a template so that sequencing is performed only on DNA that is derived from protein coding sequences of the genome. Usually only short stretches of DNA, the expressed sequence tags, are used. These ESTs usually are the first evidence of a functioning gene and are produced in huge numbers as part of the Human Genome Project.
To determine the function of the corresponding genes, antibodies against the protein fragments encoded by ESTs have to be made, and these antibodies are used as research tools - to determine the expression, location and role of the EST-encoded proteins in various tissues and developmental stages. In some cases, such antibodies may be developed as therapeutic agents.
"However, up to date five to 10 peptides have to be synthesized from each EST, and against each of the peptides an antibody has to be made," Thomas von R|den, chief scientific officer of MorphoSys, told BioWorld International.
"Usually, our customers have 300 to 500 ESTs at hand, so that the number of antibodies and corresponding screening runs is quite high," he said. "So we set out to develop an easier approach. With our novel method the generation of several peptides from ESTs is not necessary any more. Instead, we can produce antibodies in large numbers and in parallel mode directly from the polypeptides derived from the ESTs. This high-throughput approach has not been possible so far and is much faster, easier and cheaper than the conventional method."
Other efforts to speed up the process have led to methods for the automated generation of peptides from ESTs, but such procedures do not reduce the number of antibodies and screens.
Von R|den said the antibodies generated with the new method were suited not only to detect denatured proteins but also could be combined with MorphoSys' proprietary Human Combinatorial Antibody Library (HuCAL) technology to discover native proteins and to search for drug candidates. "So it is a very valuable extension of the potential of our HuCAL technology and a significant step toward our goal of linking functional genomics and drug discovery."
"We know there is a real demand from the pharmaceutical industry for high-throughput methods to generate antibodies against EST-encoded fragments," added Dave Lemus, chief financial officer of MorphoSys. "So this is a breakthrough of real significance that will increase the attractiveness of MorphoSys as a partner. The new technology not only reflects our level of sophistication, but clearly shows that the company value was not reflected in the share price so far."
Shares of MorphoSys, which had drifted below the issue price since it initial public offering in March 1999, gained 64 percent Thursday to close at EURO 23.80.