Molecular biologists have been working on making artificial antibodies for over twenty years, which come to think of it, isn’t so long. Nature took many hundreds of millions of years to develop antibodies as the natural defense of living organisms against the onslaught of antigens such as bacteria, viruses, and other damaging invaders. The only problem, at least from the human perspective, is that natural antibodies don’t always do their job; they don’t always produce the right means to attack the type of bacteria or virus. Also natural antibodies sometimes do too well, and become a source of destruction in their own right, for example with organ transplants. It would be medically very significant to be able to produce antibodies artificially, at will, and with various targeted capabilities.
The key to antibodies is the ability of an antibody molecule to have just the right configuration or shape to receive (or imprint) the target. Most invading material, bacteria or virus, has protein structures with distinctive shapes. Think of it like Lego structures with turns, L’s, arms, corners, and pockets. Antibodies have corresponding shapes that can bind (accept or receive) specific bacteria or virus shapes, after which their chemical components go to work to destroy the invader. Artificial antibodies will have to have this same capability.
The idea of using plastic (polymers) for artificial antibodies goes back many years when scientists were becoming disenchanted with using natural proteins to simulate antibodies. The natural protein structures were (and are) difficult to manipulate, not very robust, and unreliable to load with various kinds of reactive chemicals. By contrast plastic structures could be cheap, easily manipulated, quite robust within the body (that is, lasting long enough to do the job), and were generally not affected by the types of medicine loaded into them.
The ‘plastic’ of this kind falls into the category of nanomedicine because typically the polymer shapes are themselves molecules of only a few nanometers (on the order of a few 1/100,000ths of the thickness of human hair) in size. It has taken scientists a long time to master the production techniques for making polymer shapes with exactly the right configuration to attack a specific antigen.
The case in point is work done by pioneers in this field, Yu Hoshino and Kenneth Shea (University of California, Irvine, USA) in collaboration with researchers at the University of Shizuoka (Japan) and Stanford University (USA). As published in April’s issue of the Journal of the American Chemical Society, the team concentrated on the antigen melittin, a toxin found in bee stings that can be a potent (even fatal) inflammatory and cellular disruption agent. In humans, the effects of bee stings and melittin can occur long before the body can produce enough appropriate antibodies, so having an effective artificial antibody could save many lives.
The researchers used chains of polymer molecules to manufacture a shape with exactly the right indentations (“craters”) to accept the shape of the melittin toxin. The tiny, molecular, artificial antibodies were then injected into mice close to dying from a dose of melittin. The effect was strong enough to not only bind to the melittin, but also to reduce its potency and thereby increasing the probability of survival for many mice. This was a first, a live test of the plastic antibodies. As Kenneth Shea put it:
“This opens the door to serious consideration for these nanoparticles in all applications where antibodies are used,” Shea said in a prepared statement, suggesting the technique could be used to generate plastic antibodies tailored to fight any number of troublesome antigens.
[Source: Scientific American]
Perhaps they can, but a trial in mice doesn’t tell the whole story. This approach is long years away from human trials and from allaying a concern over injecting nanoparticles for such critical medicine. Nevertheless, of such steps are science made, and this is one to keep an eye on because the impact of artificial antibodies could be considerable.