Somatic cell nuclear transfer

Abstract

Nuclear transfer research became front-page news when the birth of Dolly, the cloned ewe, was reported by Ian Wilmut and Keith Campbell in 1997. Since Dolly’s birth, offspring from many other species have been produced using somatic cell nuclear transfer. While Dolly’s birth transformed embryology research, her death in February 2003 marked the beginning of the next phase of research and development. This period will determine the scale of the commercial and societal benefits that accrue from somatic cell nuclear transfer and transgenics. Proof of concept for many of the potential benefits of somatic cell nuclear transfer has already been demonstrated. Desirable genotypes have been cloned, further insights into the nuclear reprogramming process have been achieved, and precision gene insertions/deletion has been demonstrated. It is likely that nuclear transfer can be adapted to ‘copy’ individuals from any mammalian species. Offspring have been produced using cells from sheep, mice, cattle, goats, pigs, rabbits and a cat. It appears very likely that copying of other species such as horses will follow shortly. However, early results from monkeys suggest that somatic cell nuclear transfer in primates may require further intensive study before the likelihood of success can be predicted. The nuclear transfer process is far less efficient at producing healthy offspring than the natural process of combining a sperm with an egg. Fewer normal embryos, fetuses and offspring are produced from somatic cell nuclear transfer than from other assisted breeding techniques. The reasons for this appear to be related to abnormal expression of key developmental genes. Many of these genes are imprinted genes, which rely on correct methylation patterns of the genome that are established in the first week of life. Research into this area not only aids further development of the nuclear transfer technique but is also important for basic research into understanding the nuclear reprogramming process in mammals. The combination of nuclear transfer with gene insertion/deletion techniques has permitted a quantum leap in the efficiency of producing livestock with an additional ‘value adding’ gene. This has resulted in more economical production of animals that carry a specific valuable gene, such as a gene to enable production of novel or valuable proteins in their milk. Precision gene insertions or deletions will become more available in the near term so that this technique will become as important for testing gene function for agricultural applications as it is in mice for biomedical uses. Our challenge for the next decade is to fine-tune the somatic cell nuclear transfer technique so as to achieve more normal development rates. At the same time we need to increase the efficiency of targeted gene insertion or deletion so that the 2 techniques can be effectively combined to utilise the information on gene function created by livestock gene discovery programs.