Nucleic acids encoding a chimeric glycosyltransferase
AssigneeThe Austin Research Institute
InventorsIan Farquhar Campbell McKenzie, Mauro Sergio Sandrin
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Abstract
The invention relates to nucleic acids which encode glycosyltransferase and are useful in producing cells and organs from one species which may be used for transplantation into a recipient of another species. It also relates to the production of nucleic acids which, when present in cells of a transplanted organ, result in reduced levels of antibody recognition of the transplanted organ.
Claims20
A polynucleotide encoding a chimeric enzyme comprising:
- a) a glycosyltransferase localization signal directing localization of the chimeric enzyme to the Golgi of a cell;
- and
- b) a catalytic domain of a fucosyl transferase that competes with galactosytransferase for substrate.
A polynucleotide encoding a chimeric enzyme comprising:
- a) a localization signal of an alpha-1,3 galactosyl transferase enzyme;
- b) a catalytic domain of a fucosyl transferase that competes with the galactosytransferase for substrate.
A method for reducing an amount of gal-alpha-(1,3)-gal present on cells comprising:
- a) transducing the cells with a polynucleotide encoding chimeric enzyme, said chimeric enzyme comprising:
- i) a glycosyltransferase localization signal directing localization of the chimeric enzyme to the Golgi;
- and
- ii) a catalytic domain of a fucosyl transferase that competes with galactosytransferase for substrate;
- b) expressing the polynucleotide in the cells such that the chimeric enzyme is produced, wherein activity of the chimeric enzyme in the cells reduces the amount of gal-alpha-(1,3)-gal present on the cells by competing with galactosyl transferase for substrate, resulting in less substrate being converted into a gal-alpha-(1,3)-gal than in the absence of said chimeric enzyme.
A method for reducing an amount of gal-alpha-(1,3)-gal present on cells comprising:
- a) transducing the cells with a polynucleotide encoding a chimeric enzyme, said chimeric enzyme comprising:
- i) a localization signal of an alpha-1,3 galactosyl transferase enzyme;
- and
- ii) a catalytic domain of a fucosyl transferase that competes with galactosy transferase for substrate;
- expressing the polynucleotide in the cells such that the chimeric enzyme is produced, wherein activity of the chimeric enzyme in the cells reduces the amount of gal-alpha-(1,3)-gal present on the cells by competing with galactosyl transferase for substrate, resulting in less substrate home converted into gal-alpha-(1,3)-gal than in the absence of said chimeric enzyme.
Dependencies are inferred from the claim text.