The yolk of the matter

The prospect of using chicken eggs as commercial 'biofactories' for the production of protein-based drugs has moved a step closer with the announcement of a study showing that transgenic cockerels can pass on an introduced marker gene to their offspring, a milestone achievement.

The prospect of using chicken eggs as commercial 'biofactories' for the production of protein-based drugs has moved a step closer with the announcement of a study showing that transgenic cockerels can pass on an introduced marker gene to their offspring, a milestone achievement.

The development results from a collaboration between the Roslin Institute in the UK, famous for its work on cloning Dolly the sheep, Viragen of the USA and the UK's Oxford BioMedica.

The success of this preliminary 'proof-of-principle' study has sparked an exclusive licensing deal in which Viragen has obtained sole rights to proprietary gene transfer vectors, designed to transfer genes into cells at high efficiency, from Oxford BioMedica. Viragen has been collaborating with the Roslin Institute on using avian transgenics as a novel platform for the efficient, cost-effective manufacturing of protein drugs since December 2000.

Douglas Lind, Viragen's senior advisor on corporate strategy, told a conference call on 18 March that "the goal of the collaboration is to develop an alternate method of producing peptide drugs, both for Viragen's pipeline of drug candidates, as well as for industry-wide contract manufacturing."

He noted that Viragen is looking at several methods for transferring genes into chicken eggs in its avian transgenics program, but Oxford BoMedica's technology is particularly exciting. Terms of the agreement have not been disclosed.

In the study, a 'reporter gene' was used to measure the efficiency of the vectors. Chick embryos were transfected with the reporter gene carried by the vectors and analysis showed that 100 per cent of the resulting male birds possessed the gene in their sperm, meaning that they were successfully transgenic. The second stage of the study involved breeding these first generation transgenic cockerels to determine the frequency of transgenic birds in the next generation.

Helen Sang, a leading expert on avian biology based at the Roslin Institute, told the conference call that the frequency of transgenic offspring was between one in 100 and one in three, a frequency far exceeding requirements for commercial viability and higher than previously-published approaches.

"We introduced the Oxford BioMedica vectors into chick embryos and raised hatched chicks for breeding. Nine developed into adult transgenic roosters, indicating that stable transfection had been consistently achieved. We then bred from these roosters to determine the frequency of transgenic offspring produced. Each rooster successfully produced transgenic offspring, with frequencies ranging from 1 per cent to 29 per cent of the chicks hatched transgenic," said Sang.

Noting that these are potentially breakthrough findings, Sang said that the next stage of the project is to apply the technology to the production of an antibody intended as a treatment for the skin cancer malignant melanoma.