The cost and levels of protein production in birds (i.e. chickens) rivals that of mammals and can provide an alternative for proteins that are not suitable for production in ungulates. ⁽³⁾ In addition, due to the short generation time and ease of breeding, chickens offer rapid and scaleable bioreactor capabilities.

Avian transgenesis lags behind that of mammals as retroviral-mediated transgenesis is still the most efficient method and microinjection is very inefficient. NT in avians poses a different set of problems, due to the large size of the yolk on which the oocyte resides. This makes manipulation of the oocyte difficult and visualization of the metaphase plate even harder. Nevertheless these limitations can be overcome.

Embryonic stem (ES) cells are early embryonic cells that are able to remain totipotent after many generations in vitro and have enabled gene targeting in mice, but not in any other species. ES-like cells isolated from non-mice mammalian species and cultured for any period of time (especially after the first passage) often are able to contribute to somatic but not germline tissues, yielding low-value chimeric animals. Avian-derived ES-like cells have never been conclusively shown to contribute to somatic and germline tissues of recipient embryos. NT appears to offer a solution to this dilemma but the long-term culture of cells able to act as nuclei donors suffers the same problem.

Currently nuclei from fetal tissues serve as the best donors in mammalian NT (see ⁽⁷⁾ for review). However when cultured for the periods of time required for gene targeting, the cells lose the ability to serve as donors. Recent work in mice improved upon the efficiency of NT but the donor cells (cumulus) were not cultured. ⁽⁸⁾ Thus there may be a need to identify culture conditions that allow long term culture and gene targeting of NT donor cells. Such culture conditions may overlap with those needed for ES cells, therefore the advent of NT does not eliminate the need for development of ES cell technologies in animal transgenesis. As an alternative, new methods could be developed to target genes in the short culture times currently available.

ATP is an ideal support platform for the development of such techniques as they are indeed cutting edge, high risk and fraught with unforeseen pitfalls. The benefits of such technologies will have revolutionary impacts in the healthcare and agricultural industries as well as spur new research in all fields of biology and medicine.

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5. K. H. Campbell, J. McWhir, W. A. Ritchie, I. Wilmut, Nature 380, 64-6 (1996).

6. I. Wilmut, A. E. Schnieke, J. McWhir, A. J. Kind, K. H. Campbell, Nature 385, 810-3 (1997).

7. G. B. Anderson, G. E. Seidel, Science 280, 1400-1 (1998).