Cattle antibody production moves a step closer
system for making unlimited quantities of antibody-based drugs for
human applications in cattle.
The scientists, from US company Hematech, have genetically engineered calves that carry copies of human genes for the heavy and light chains of antibodies, but lack the genes for the bovine antibody heavy chain. Hematech has received an unspecified milestone payment from its partner, Japan's Kirin Brewery, on the back of the achievement.
The bovine production system is created by introducing the sequences for both the human heavy and light chain antibody genes into cows, using a human artificial chromosome (HAC) vector developed at Kirin. The HAC is inserted into bovine foetal fibroblast cells and cloned cattle are produced from the modified cells.
Hematech has shown that the human chromosome fragment is retained in the cloned cattle and undergoes normal processing, with human antibody proteins detected and collected from the blood of newborn calves.
By knocking out both copies of the bovine immunoglobulin gene, the company has been able to reduce the amount of circulating bovine antibodies in the blood. Because these antibodies would see a human type antibody as foreign and neutralise it, this reduction should increase the yield of human polyclonal antibody product.
Tackling the TSE issue
One concern with using cattle to make antibodies is the risk of contamination with the agents - called prion proteins - that cause transmissible spongiform encephalopathies, such as BSE in cattle and CJD in humans.
However, Hematech believes it has bypassed this obstacle by using its technology to engineer an embryo that lacks the genes required to make prion proteins and perpetuate the disease.
"If live animals are produced from these embryos they will be prion free and thus unable to contract mad cow disease," said James Barton, Hematech's chief executive. "These animals will be ideal for the production of the companies' fully human polyclonal antibodies," he said.
The sequential gene targeting technology that enabled Hematech to knock out the bovine heavy chain antibody genes will be published by researchers from Hematech and Kirin in the June 6 advanced online publication section on the Nature Genetics website.
