Egg-based protein production moves forward
to try to overcome the primary obstacles to producing recombinant
proteins in eggs, the low level of expression of the gene
transcript coding for the target protein and difficulties getting
the trait passed on to offspring.
Under the terms of the alliance, Florida-based Viragen has taken out a license for an expression vector system developed by Oxford Biomedica called LentiVector, which is claimed to boost the efficiency of making transgenic birds 10-100 fold compared to vector systems based on oncogenic retroviruses.
The companies had been working together with the Roslin Institute in Scotland - where the cloning of Dolly the sheep took place - to apply the LentiVector technology to the production of transgenic broods of chickens as a novel platform for the efficient and economical manufacturing of therapeutic proteins, and the latest development marks the first commercial arrangement between the parties.
The use of poultry to make proteins has been mooted for some time. The idea is to genetically modify the birds at the embryonic stage using DNA microinjection - a process that is of course much easier in birds than mammals as they lay eggs externally - so that they produce a desired protein in the white of their eggs that can be harvested and purified.
Early experiments with oncogenic retroviruses were disappointing, because although transgenic birds were produced it occurred at a low frequency and protein expression was poor. The use of Oxford Biomedica's LentiVector aims to tackle both these problems.
In initial tests, Viragen, the Roslin and Oxford Biomedica created 12 transgenic cockerels expressing a reporter gene using the LentiVector technology, all of which were transgenic. 10 of them were bred, and transmitted the trait to between 4 per cent and 45 per cent of their chicks. Moreover, the reporter gene (either lacZ or green fluorescent protein) was found in second and third generation birds and appeared to have no adverse effect.
"This frequency of production of transgenic birds is 10-100-fold higher than obtained using other viral vectors or other, unrelated methods for genetic modification," according to Helen Sang of the Roslin Institute, who led the project.
"Manufacturing protein-based drugs through an avian transgenic expression system should offer certain advantages to traditional production systems - likely in terms of speed, efficiency and cost," said Viragen's chief executive Charles Rice.
Under the terms of the agreement, Oxford BioMedica receives an undisclosed upfront license fee and annual maintenance payments. In addition, the UK firm will receive milestone payments on the achievement of technical goals by Viragen and royalties on commercialisation of the technology.
