Methods for treating blood coagulation disorders

Abstract

The present invention relates to a method of treating an individual having a blood coagulation defect (e.g., hemophilia A, hemophilia B), comprising administering to the individual an effective amount of a DNA vector encoding modified Factor VII (FVII), wherein the modified Factor VII leads to generation of Factor VIIa in vivo. In a particular embodiment, the invention pertains to a method of treating an individual having a blood coagulation defect comprising administering to the individual an effective amount of a nucleic acid encoding a modified FVII wherein the modified FVII comprises a signal which codes for precursor cleavage by furin at the activation cleavage site of the modified FVII. The invention also relates to a method of treating an individual having a blood coagulation disorder comprising administering to the individual an effective amount of a nucleic acid encoding the light chain of human FVII and a nucleic acid encoding the heavy chain of human FVII operably linked to a leader sequence. Compositions, expression vectors and host cells comprising nucleic acid which encodes a modified Factor VII, wherein the modified Factor VII leads to generation of Factor VIIa in vivo is also encompassed by the present invention.

1 . A method of promoting blood coagulation in an individual having a blood coagulation defect and in need thereof, comprising administering to the individual a blood coagulation enhancing effective amount of a DNA vector encoding a Factor VII polypeptide that can be converted to Factor VIIa when expressed in said individual, said Factor VII polypeptide comprising an enzymatic cleavage site susceptible to cleavage by furin, whereby cleavage by furin produces Factor VII heavy chain and Factor VII light chain molecules.