Materials and methods for management of hyperacute rejection...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/54 (2006.01) A01K 67/027 (2006.01) A61K 31/70 (2006.01) A61K 35/12 (2006.01) A61K 35/16 (2006.01) C07K 14/52 (2006.01) C07K 14/54 (2006.01) C07K 16/40 (2006.01) C12N 5/10 (2006.01) C12N 9/10 (2006.01) C12N 15/19 (2006.01) C12N 15/85 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2181433

Human pre-formed xenoatibodies play an important role in the hyperacute rejection response response in human xenotransplantation. Disclosed are materials and methods for removing or neutralizing such antibodies. Also disclosed are materials and methods for reducing or eliminating the epitopes in the donor organs that are recognized by such antibodies. Such epitopes are formed as the result of activity by the enzyme .alpha.- 1,3 galactosyltransferase. The porcine gene encoding .alpha.- 1,3 galactosy transferase is disclosed, as are materials and methods for inactivating ("knocking out") the .alpha.-1,3 galactosyltransferase gene in mammalian cells and embryos. Included are nucleic acid constructs useful for inactivating the .alpha.-1,3 galactosyltransferase gene in a target cell .Also disclosed is a novel leukemia inhibitory factor (T-LIF) that is useful for maintenance of embryonic stem cells and primordial germ cells in culture.

Des hétéro-anticorps humains préformés jouent un rôle important dans les réactions de rejet hyperaigu suite à une hétérogreffe chez l'homme. Des substances et des procédés permettant de supprimer ou de neutraliser ces anticorps sont décrits, ainsi que des substances et des procédés permettant de réduire ou de supprimer les épitopes dans les organes donneurs qui sont reconnus par de tels anticorps. Ces épitopes résultent de l'activité de l'enzyme .alpha.-1,3 galactosyltransférase. Le gène de porc codant l'.alpha.-1,3 galactosyltransférase est également décrit, ainsi que des substances et des procédés permettant d'inactiver (d'éliminer) le gène .alpha.-1,3 galactosyltransférase dans des cellules et des embryons de mammifères. Sont également compris, des produits de recombinaison d'acide nucléique aptes à inactiver le gène .alpha.-1,3 galactosyltransférase dans une cellule cible, ainsi qu'un nouveau facteur d'inhibition de leucémie (T-LIF) permettant de maintenir en culture les cellules souches embryonnaires et les cellules germinales primordiales.

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