SCIENTISTS AT THE ROSLIN INSTITUTE PUBLISH SCIENTIFIC BREAKTHROUGH Ð ability to clone sheep through nuclear transfer from somatic cells
NEWS RELEASE 24 FEBRUARY 1997
For further information contact: Roslin Institute, Wendy Cuthbertson +44 (0) 1315274469
De Facto Consultants, Susan Charles, Managing Director +44 (0)1256 842274

Roslin, Midlothian, UK... The Roslin Institute and PPL Therapeutics have published in Nature (.....) the successful breeding of cloned sheep through nuclear transfer from differentiated foetal and adult cells. This is a major scientific breakthrough as it is the first time that any mammal has been derived from foetal or adult cells. The research also confirmed the ability of nuclear transfer to work with cells from embryos. Benefits of the technology could include improvements in conventional animal breeding as well as in the biopharmaceutical industry.

This work, carried out jointly by scientists from the Roslin Institute and PPL, demonstrates the ability to take cells from adult sheep mammary tissue, culture these in vitro, transfer the nucleus from one of these cells to an enucleated egg which is then implanted in a surrogate mother and leads to the birth of a healthy lamb which is genetically identical to the sheep from which the mammary cells were taken. This is a further advance of the nuclear transfer technology published by scientists from Roslin last year (Nature 380, 64-66, 1996)

Scientifically this work clearly demonstrates the effectiveness of nuclear transfer in overcoming the processes responsible for the normal differentiation of cells and may eventually allow offspring to be obtained from a variety of donor cells, some taken directly from adult animals. It also demonstrates that no genetic information was lost or inactivated during the development of the donor cells.

ÒAnimal breeding companies are already showing interest in the use of this technology to multiply their best animalsÓ said Dr Ian Wilmut, leader of the research team at the Roslin Institute. ÒIt takes many years for animal breeders to transfer the progress they make in elite selection herds to the commercial farmer. A limited amount of cloning could speed this process up substantially, bringing the meat or milk yield of the average cow or sheep closer to that of the best.Ó

Many drugs that are derived from human proteins cannot be made in sufficient quantities to meet clinical demand and PPL Therapeutics are already making transgenic sheep and cattle to produce human proteins in their milk. ÒThe new nuclear transfer technology will allow transgenic animals to be produced more cheaply. Genetic modification of the donor cells in culture before they are used in nuclear transfer will also allow us to introduce very precise changes in their DNA and open up the possibilities for a range of new products for the treatment of, for example, cancer and inflammationÓ said Dr Wilmut. He thought it unlikely, however, that this new technology would be used in the foreseeable future to produced genetically modified animals with improved meat or milk yields.
- press release ends-


PPL THERAPEUTICS
PRESS RELEASE
ON JUNE 11TH 1996 PPL was floated on the London stock exchange. Shares were initially traded at a value of £4.50, giving an overall valuation of >£100m.

PPL was started in 1987 with a single employee to commercialise technology developed by Dr John Clark and his colleagues at the then Animal Breeding Research Organisation. PPL now has over 120 employees, with headquarters and main laboratories at Roslin. PPL activities are based on 4 patents taken out by the Institute that cover methods for targeting gene expression to the mammary gland and in particular, the use of beta-lactoglobulin promoter.

In 1993, PPL merged with TransPharm Inc (now PPL Inc) of Blacksburg, Virginia, a company that had been created to commercialise the transgenic expertise of the Virginia Polytechnic Institute and State University. Work in the U.S. primarily involves transgenic cows and pigs, whereas that in the UK is largely concerned with sheep. A purification plant build to GMP standards is now operational in Scotland and is being used for larger scale purification of alpha1-antitrypsin from milk, in preparation for clinical trials.

PPLÕs business strategy is to focus on the supply of human proteins for the treatment of medical conditions where the supply is currently limited and/or the product is expensive to produce. Many of PPL candidate proteins are produced by other routes (e.g. blood fractionation) and have already been approved for use in humans or are in clinical trials. This should reduce the risk of clinical failure compared to that faced by pharmaceutical companies producing entirely new drugs and offer a shorter time to market.

To date, PPL have produced over 20 different proteins in the milk of transgenic animals. Product development programmes are well advanced for alpha1-antitrypsin (cystic fibrosis), activated protein C (prevention of deep vein thrombosis), fibrinogen (tissue glue for trauma and surgical procedures), factor VIIa (for a variety of bleeding complications) and factor IX (for therapeutic treatment of haemophilia B). Clinical trials of alpha1-antitrypsin from the milk of transgenic sheep are due to start shortly, with approval for its use for treatment in cystic fibrosis projected for 2001.
end press release