Designing antibodies. Problems and ideas?

[Genecks]

I've recently been assigned the task of making a decent antibody for amyloid precursor protein (and perhaps something else, too). As I have been reading as of late, there is considerable demand for decent antibodies, as people don't tend to like what comes from industry.

 

First off, why?

 

Does industry not put enough effort into making antibodies, such as generating one generation of a mouse population to produce antibodies, thus the search for better antibodies beyond that one generation does not occur? Industry would be the social structure with enough money to improve on design rather than independent academic institutions, right?

 

Is it that industry isn't really looking for better antibodies?

 

The individual I'm working for at the moment doesn't seem to like the current quality of antibody on the market and being used for our research, so I've been assigned to make antibodies.

 

As of late, I've been reading the book Making and Using Antibodies: A Practical Handbook.

 

It seems like there are two reasonable ways to make antibodies: Mutation/radiation/conjure-code OR to inject animals with the immunogen and have the animals keep producing antibodies.

 

It seems to me that animals that could live a long time in order to produce antibodies might be the best bet in terms of finding a better antibody with binding affinity. Am I right on this?

 

Also, I suspect if a person was a super scientist with an insane knowledge of biophysics, chemistry, and protein knowledge, a person could just design a better antibody from code... but I suspect that would mean knowing the protein being research, and the protein being research in this case is ... the structure is not completely known...

 

So, why do scientists think most antibodies are poor? Are they? Why?

Edited March 30, 2012 by Genecks

[ecoli]

Generally, a poor antibody will have poor binding affinity to the target antigen or has too much cross reactivity to off-target effectors. Since the animal making the antibody is not usually the same as the model system the researcher is using the antibody in, unpredictable off-target effects are especially problematic.

[CharonY]

It is very tricky to impossible to "design" antibodies from scratch. It would require the knowledge of the 3D structure of the target and especially of the epitopes under quite a bit of different conditions (the structure of proteins is rather dynamic and highly dependent on its environment). For this reason, even having a crystal structure would not automatically solve the problem. Plus, you got the precise problem on the antibody side, of course. And finally the binding is often not absolutely specific, as ecoli pointed out.