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COMPOSITIONS AND METHODS FOR PRODUCTION OF AGLYCOSYLATED PLASMINOGEN
专利权人:
发明人:
申请号:
HK12109746.4
公开号:
HK1169141A
申请日:
2012.10.04
申请国别(地区):
HK
年份:
2013
代理人:
摘要:
Compositions and methods for producing aglycosylated plasminogen (PLG) polypeptides and fragments and variants thereof are provided. Compositions of the invention include isolated nucleic acid molecules encoding aglycosylated PLG polypeptides in which the asparagine (Asn) residue corresponding to residue Asn-289 of the mature human PLG polypeptide has been substituted with an amino acid residue that does not support N-linked glycosylation at that position of the PLG polypeptide, as well as the aglycosylated PLG polypeptides encoded thereby. Expression constructs comprising these PLG-encoding nucleic acid molecules and transgenic plants comprising these expression constructs are also provided. Methods of the invention comprise introducing a PLG-encoding nucleic acid molecule of the invention into a plant of interest and culturing the plant under conditions to produce the aglycosylated PLG polypeptide. The aglycosylated PLG polypeptide allows for significant increases in production and yield of PLG from a plant-based expression system without comprising the ability of the PLG product to be activated to a polypeptide capable of binding fibrin and having serine protease activity, including biologically active plasmin that is also aglycosylated. The activated aglycosylated plasmin is useful to treat diseases or conditions associated with a thrombus.La présente invention concerne des compositions et des procédés permettant la production de polypeptides aglycosylés du plasminogène (PLG), ainsi que de fragments et de variantes de ceux-ci. Les compositions de linvention comprennent des molécules dacides nucléiques isolées codant pour des polypeptides PLG aglycosylés dans lesquels le résidu dasparagine (Asn) correspondant au résidu Asn-289 du polypeptide PLG humain mature a été remplacé par un résidu dacide aminé ne supportant pas de glycosylation N-liée dans cette position du polypeptide PLG, ainsi que des polypeptides PLG aglycosylés ainsi encodés. Linvention concerne égale
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