(Page 2 of 2)
Shea's plastic antibody targeting melittin performed well in test tubes, but there was still some skepticism whether it would work in the complex environment of the body. This month in Journal of the American Chemical Society, the University of California researchers describe promising studies in mice. The researchers attached different fluorescent imaging probes to melittin and to the plastic antibody, injected them into the mice, and watched what happened in real time. Because the probes were two different colors, the researchers were able to watch as the polymer met its target in vivo, and as the two were then cleared to the liver. In mice given only the toxin and not the antidote, the mice's symptoms were much worse, and the toxin was more widely distributed throughout the body.
"They show that these materials are biocompatible and really act like antibodies--it's kind of surprising," says Ken Shimizu, professor of biochemistry at the University of South Carolina. Researchers had suspected that the body might not recognize the plastic particles as antibodies and thus they would be ineffective, or that they might get gummed up with other particles in the complex mixture that is the bloodstream.
Shea says that he's been contacted by several pharmaceutical companies that are interested in seeing how the work develops. David Spivak, professor of chemistry at Louisiana State University, agrees that the method is "a general strategy that will work again and again." "These particles have huge advantages in terms of stability and low cost," says Spivak. "I just hope this work is reproducible for many different targets."
The California researchers developed their imprinting methods using melittin because it's relatively inexpensive and easy to obtain, and it's a good representative of a class of small protein toxins, some of which are much more deadly. "Our next steps are to pursue more serious toxins," says Shea.
Artificial antibodies could sniff out viruses and toxins
So these antibodies meet their target and then go to the liver. I'm not aware of liver being able to break down plastic into reusable or non-toxic components. Wouldn't they cause liver damage negating their positive effect?
My question exactly--what happens in the liver? Can the body (at least of a mouse) safely clear these complexes?
And what uses do the researchers envision: strictly using these plastic antibodies as anti-venins/anti-toxins, or could they be used to treat cancer, autoimmune diseases, and other conditions as biofactured antibodies are?
The plastic antibodies would have to be designed to be broken down as a water soluble glucuronide, (or some other form) which than can be excreted in the urine.
The liver does this all the time with many natural chemicals such as hemoglobin, and "natural" antibiotics.
Other issues include Absorption by the Gut so oral meds could be given,(If not, given by IV or IM) and lastly, the ability to cross the blood brain barrier, for brain infections; and toxicity issues would have to be addressed,... just like the medicines that we take today.
This is exciting. There is no reason that a designer antibiotic could be made on demand, (in a relatively short time) for the ever increasing multiple resistant antibiotics that we see today. Other uses are mentioned above.
Ron Hansing 6.15.10
"The new immunology graduate was given advice by the older man - I have one word for you, my boy, Plastic; yes Plastics – that’s the future of immunology!"
Well maybe, but maybe not. The previous commenters have raised a key question about this new approach, which raises two more questions: a) what are the polymers used; and 2) what happens to them in the liver. I've read the original paper Hoshino, Kodama, Okahata, and Shea. It describes the polymers as "acrylamides such as N-isopropylacrylamide”. They synthesized various copolymers using different types of substituted acrylamides. There have been some studies showing harmful effects of acrylamides. However, it’s important to keep in mind that “the dose makes the poison”. The harmful effects of acrylamides may occur at concentrations greater than would be involved in using such molecules as synthetic antibodies. Also, there is the issue of the particular metabolic pathways involved. Perhaps someone who understands liver biochemistry, e.g., the last commenter, could help us out here.
Anyway, the article in JACS focused mainly on how the polymer composition was adjusted to optimize binding to the antigen. They also determined that the antibody-antigen complex had little or no interaction with blood components: albumin and fibrinogen. There was no discussion about toxicity or liver metabolism. The authors described the results as a starting point for the preparation and evaluation of synthetic antibodies for key antigens. I’m guessing that if the idea pans out, and if the polymers they used pose a toxicity problem, other polymers could be synthesized that avoided the problem.
This is cool stuff! I wonder if these MIPs could be used as a vaccine to prompt the body to make natural antibodies.
Manufacturing in the United States is in trouble. That's bad news not just for the country's economy but for the future of innovation.
On Twitter
Become a Fan on Facebook
Subscribe to the Feed
drothman911
2 Comments
Interesting, probably valuable, not exactly new
The idea of plastics mimicing antibodies is not new. We were making such polymers in an industrial research lab in the mid-1990's, based on earlier published work from Sweden.
A book on the subject: Molecularly Imprinted Polymers, 23 edited by B. Sellergren
Hardbound, 582 pages
Published: DEC-2000
ISBN 10: 0-444-82837-0
ISBN 13: 978-0-444-82837-8
Imprint: ELSEVIER
Reply