Production of mature proteins in plants

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/82 (2006.01) C07K 14/765 (2006.01) C07K 14/81 (2006.01) C12N 9/54 (2006.01) C12N 15/14 (2006.01) C12N 15/15 (2006.01) C12N 15/57 (2006.01) C12P 21/02 (2006.01)

Patent

CA 2280894

A method for producing one of the following proteins in transgenic monocot plant cells is disclosed: (i) mature, glycosylated .alpha.1-antitrypsin (AAT) having the same N-terminal amino acid sequence as mature AAT produced in humans and a glycosylation pattern which increases serum halflife substantially over that of mature non-glycosylated AAT; (ii) mature, glycosylated antithrombin III (ATIII) having the same N-terminal amino acid sequence as mature ATIII produced in humans; (iii) mature human serum albumin (HSA) having the same N-terminal amino acid sequence as mature HSA produced in humans and having the folding pattern of native mature HSA as evidenced by its bilirubin-binding characteristics; and (iv) mature, active subtilisin BPN' (BPN') having the same N-terminal amino acid sequence as BPN' produced in Bacillus. Monocot plants cells are transformed with a chimeric gene which includes a DNA coding sequence encoding a fusion protein having an (i) N- terminal moiety corresponding to a rice .alpha.-amylase signal sequence peptide and, (iii) immediately adjacent the C-terminal amino acid of said peptide, a protein moiety corresponding to the mature protein to be produced.

L'invention concerne un procédé servant à la production de l'une des protéines suivantes dans des cellules de plantes monocotylédones transgéniques: (1) .alpha.¿1?-antitrypsine (AAT) glycosylée mature comportant la même séquence d'acides aminés N-terminaux que l'AAT mature produite par l'homme, et un motif de glycosylation permettant d'accroître sensiblement la demi-vie de sérum par rapport à celle d'AAT non glycosylée mature; (2) antithrombine III glycosylée (ATIII) mature comportant la même séquence d'acides aminés N-terminaux que l'ATIII produite par l'homme; (3) albumine sérique humaine (HSA) mature comportant la même séquence d'acides aminés N-terminaux que l'HSA mature produite par l'homme, et présentant le même motif de repliement que l'HSA mature native, comme le montrent ses caractéristiques de fixation de bilirubine; et (4) subtilisine BPN' (BPN') active mature présentant la même séquence d'acides aminés N-terminaux que la BPN' produite par Bacillus. Des cellules de plantes monocotylédones sont transformées à l'aide d'un gène chimère comportant une séquence codante d'ADN codant pour une protéine de fusion possédant (1) une fraction N-terminale correspondant à un peptide signal d'.alpha.-amylase de riz, et (2) immédiatement adjacente à l'acide aminé C-terminal dudit peptide, une fraction de protéine correspondant à la protéine mature à produire.

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