Suppression of Galα1-3Gal expression by antisense oligonucleotides specific for porcine α-1, 3-galactosyltransferase mRNA treatment
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概要
- 論文の詳細を見る
One of the big problems in xenotransplantation from pigs to humans is the hyperacute immune reaction due to the carbohydrate epitope of Galα1-3Gal. Based on the porcine α-1, 3-galactosyltransferase cDNA sequence, several antisense oligonucleotide DNAs (20-base pair phosphorothioates) were chemically synthesized and used to suppress the expression of the Galα1-3Gal carbohydrate epitope on the surface of a porcine kidney cell line. One of the antisense oligonucleotide cDNAs including the stop colon of the sequences, caused a significant 30 to 35% decrease in the level of expression compared to in untreated cells. However, the treatment had no effect on cell growth and exhibited no toxicity. In contrast, the corresponding sense oligonucleotide or other antisense oligonucleotides containing the 5-start colon had no effect on the carbohydrate expression. The binding of cells to human serum was investigated after the effective antisense oligonucleotide treatment. Cells thus treated were less reactive to human IgG or IgM. This evidence strongly supported that natural antibodies contained in human serum became less reactive with these cells due to suppression of Galα1-3Gal carbohydrate epitope expression on the cell surface by antisense oligonucleotide treatment. These findings provide a basis for and a means of genetic manipulation of porcine α-1, 3-galactosyltransferase for future xenotransplantation studies.
- 日本学士院の論文
著者
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HANDA Shizuo
Department of Biochemistry, Faculty of Medicine, Tokyo Medical and Dental University
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Handa Shizuo
Department Of Biochemistry Faculty Of Medicine Tokyo Medical And Dental University
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Kushi Yasunori
Department Of Biochemistry Faculty Of Medicine Tokyo Medical And Dental University
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Taguchi Akiko
Department Of Neuroanatomy Osaka Univ. Medical School
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Arita Masanobu
Department Of Food And Nutrition Tokyo-kasei University
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TAGUCHI Akiko
Department of Food and Nutrition, Faculty of Home Economics, Tokyo Kasei University
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KUSHI Yasunori
Department of Agricultural and Life Science, Obihiro University of Agriculture and Veterinary Medicine
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