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- Carol J. Phelps
- PPL Therapeutics Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA.
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- Chihiro Koike
- Thomas E. Starzl Transplantation Institute,
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- Todd D. Vaught
- PPL Therapeutics Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA.
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- Jeremy Boone
- PPL Therapeutics Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA.
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- Kevin D. Wells
- PPL Therapeutics Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA.
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- Shu-Hung Chen
- PPL Therapeutics Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA.
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- Suyapa Ball
- PPL Therapeutics Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA.
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- Susan M. Specht
- Thomas E. Starzl Transplantation Institute,
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- Irina A. Polejaeva
- PPL Therapeutics Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA.
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- Jeff A. Monahan
- PPL Therapeutics Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA.
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- Pete M. Jobst
- PPL Therapeutics Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA.
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- Sugandha B. Sharma
- Thomas E. Starzl Transplantation Institute,
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- Ashley E. Lamborn
- PPL Therapeutics Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA.
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- Amy S. Garst
- PPL Therapeutics Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA.
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- Marilyn Moore
- PPL Therapeutics Ltd., Roslin, Midlothian, EH25 9PP, UK.
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- Anthony J. Demetris
- Thomas E. Starzl Transplantation Institute,
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- William A. Rudert
- Thomas E. Starzl Transplantation Institute,
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- Rita Bottino
- Thomas E. Starzl Transplantation Institute,
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- Suzanne Bertera
- Thomas E. Starzl Transplantation Institute,
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- Massimo Trucco
- Thomas E. Starzl Transplantation Institute,
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- Thomas E. Starzl
- Thomas E. Starzl Transplantation Institute,
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- Yifan Dai
- PPL Therapeutics Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA.
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- David L. Ayares
- PPL Therapeutics Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA.
説明
<jats:p>The enzyme α1,3-galactosyltransferase (α1,3GT or GGTA1) synthesizes α1,3-galactose (α1,3Gal) epitopes (Galα1,3Galβ1,4GlcNAc-R), which are the major xenoantigens causing hyperacute rejection in pig-to-human xenotransplantation. Complete removal of α1,3Gal from pig organs is the critical step toward the success of xenotransplantation. We reported earlier the targeted disruption of one allele of the α1,3GT gene in cloned pigs. A selection procedure based on a bacterial toxin was used to select for cells in which the second allele of the gene was knocked out. Sequencing analysis demonstrated that knockout of the second allele of the α1,3GT gene was caused by a T-to-G single point mutation at the second base of exon 9, which resulted in inactivation of the α1,3GT protein. Four healthy α1,3GT double-knockout female piglets were produced by three consecutive rounds of cloning. The piglets carrying a point mutation in the α1,3GT gene hold significant value, as they would allow production of α1,3Gal-deficient pigs free of antibiotic-resistance genes and thus have the potential to make a safer product for human use.</jats:p>
収録刊行物
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- Science
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Science 299 (5605), 411-414, 2003-01-17
American Association for the Advancement of Science (AAAS)