Just parking. This is a bit old, but interesting background stuff -
Novel human antibodies have enormous potential as therapeutic agents and
research tools, but they are notoriously difficult to produce. They are
particularly useful for the detection of specific molecules, and a good
method to produce random antibody libraries would mean that "more substances
could be analyzed, which is valuable in the area of proteomics, where there
is a need for massive analyses," says Dr. Eskil Söderlind, Director of
Technology Application at BioInvent Therapeutic (Lund, Sweden).
Techniques to produce human antibodies from antibody libraries have been
around for about ten years, but they have some disadvantages. Some
techniques take antibody genes isolated from human B cells and randomly
combine these to form the six complementarity determining regions
(CDRs)--amino acid sequences that occupy the tips of antibodies and interact
directly with the target, thus dictating an antibody's specificity. Such
methods provide novel antibodies that usually fold correctly, but the
diversity of the resulting antibodies is somewhat limited because three
randomized CDRs are produced in two separate groups, then combined to form a
complete antibody. Other methods introduce a technical solution to this
problem by using synthetic antibody fragments that are designed and created
in the laboratory. This approach yields novel antibody sequences but it also
produces unnatural antibodies that may not fold properly, and which may
themselves draw an immune response.
Söderlind and his colleagues have developed a technology that allows them to
vary all six CDRs of an antibody simultaneously into one single antibody
framework. The result is a much larger range of potential recombinations,
yielding antibody libraries with high genetic diversity--and since all of
them originate from the human immune system, the potential for an immune
reaction is minimal.
"No technology has been available to achieve this combination of six natural
CDRs. There have been discussions about whether one single framework
immunoglobulin scaffold could hold all possible antibody specificities: We
have demonstrated that one single framework indeed can contain all possible
specificities. This is totally new from a scientific point of view," says
Söderlind.
Söderlind and his colleagues used the method to create antibodies that
recognize carbohydrates, which has been very difficult to do using other
systems. They also obtained extremely high-specificity antibodies--some with
sub-nanomolar ranges. That has only been achieved with larger libraries.
"In other words, we have a smaller library that performs as a larger
library. Thus, creating a larger library based on our concept would most
probably give antibodies with even higher affinities," says Söderlind.
"The antibodies can be used to detect and analyze a huge spectrum of
different substances. This is nothing new. The new thing is the speed by
which the antibodies are produced and specially the quality of them," says
Söderlind.
Reference: "Recombining germline-derived CDR sequences for creating diverse
single-framework antibody libraries," E Söderlind, L Strandbert, P Jirholt,
N Kobayashi, V Alexeiva, A-M Åberg, A Nilsson, B Jansson, M Ohlin, C
Wingren, L Danielsson, R Carlsson & CAK Borrebaeck, Nature Biotechnology,
vol. 18, no. 8, p. 852-856.
An abstract of this article can be viewed at:
nature.com
Also see -
bioinvent.com |
