Antibodies have DNA

Antibodies in the laboratory: more quality through DNA technology

Antibodies recognize foreign invaders (bacteria and viruses) and fight against them in our body. Antibodies have become indispensable as therapeutic agents in medicine and as reagents in basic biological and biomedical research - antibodies are important tools in laboratories.

Now Andrew Bradbury from Los Alamos National Labs, USA and Andreas Plückthun from the Biochemical Institute of the University of Zurich write that the quality of the commercial antibodies routinely used for research is inadequate: «Of 6000 commercial antibodies tested, only 3000 recognize their target molecule at all» , says the biochemist at the University of Zurich.

With over 100 co-signatories, they discuss the enormous problems that would arise "from unreproducible experiments and waste of time and material". The authors calculated that US $ 350 million is spent each year on unsuitable antibody reagents, and they suggest similar numbers in Europe. They are convinced that antibodies produced using recombinant DNA technology and other recombinant binding proteins would be the solution to this problem.

Many monoclonal antibodies also have deficits

Monoclonal antibodies are usually produced by a fusion of anti-body-producing B cells with tumor cells after immunization of a mouse. This creates so-called hybridoma cells that produce monoclonal antibodies. With the invention of this monoclonal anti-body technology, many researchers thought, the problem of lack of specificity was finally solved.

Far from it: It has been shown that monoclonal antibodies can often recognize several antigens, and that many hybridomas can secrete more than one antibody and also die, which means that an antibody can be lost forever. Inadequate characterization and inadequate documentation by the manufacturers as well as by the researchers about the antibodies used exacerbate the situation - with the result: Many antibodies do not recognize their alleged target molecule specifically, experiments flop or cannot be replicated.

DNA technology can solve problems

Bradbury, Plückthun and colleagues advocate producing antibodies using recombinant DNA technology, i.e. on the basis of artificially assembled DNA. With the advantage: "Once you know the DNA of an antibody, anyone can use this information to create it again at any time," explains Andreas Plückthun, a pioneer in recombinant antibody technology.

"Nowadays, therapeutic antibodies are all produced with recombinant DNA technology, characterized extremely precisely and are therefore of very high quality." Unfortunately, however, these recombinant technologies have not yet succeeded in conquering the reagent market, because the companies with the corresponding know-how have turned to the more lucrative therapeutic market.

Research has to be reproducible

What should happen? "In the long term, the DNA sequences of the reagents used in research should be publicly available, and the reagents should be produced using methods of recombinant DNA technology," explains Plückthun. This would mean that the companies that now manufacture classic reagent antibodies would have to adapt their business models, but the reproducibility of biological research simply had to be guaranteed. "There is no real alternative to recombinant DNA technology."

In a first step it is therefore important to invest in research into the efficient production of recombinant antibody reagents and similar recombinant proteins. The UZH biochemist is convinced that these are currently not cheaper to generate than traditional monoclonal antibodies, but they have enormous potential thanks to new technologies and automation. "Perhaps in ten years' time the problems caused by poorly characterized monoclonal antibodies will be a thing of the past."

Literature:
A. Bradbury, A. Plückthun and 110 co-signatories. Standardize antibodies used in research, Nature, February 4, 2014. http://nature.com/articles/doi:10.1038/518027a

A. Bradbury, A. Plückthun and 110 co-signatories. Standardize antibodies used in research, Nature, February 4, 2014. http://nature.com/articles/doi:10.1038/518027a

Contact:

Prof. Andreas Plückthun
Biochemical Institute
University of Zurich
Tel: +41 44 635 5571
Email: [email protected]

http://www.mediadesk.uzh.ch

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