Skip to content
Login Register

#Factor VIII

2 public questions tagged with this topic.

Gene Therapy

Factor VIII recombinant protein is commonly produced in:

Coagulation factor VIII complex multidomain glycoprotein organized signal peptide 19 residues followed domains A1 a1 A2 a2 B a3 A3 C1 C2 totaling 2351 aa 280 kDa requiring extensive co-translational post-translational processing secretory pathway. Nascent polypeptide translocates Sec61 translocon ER lumen signal peptidase cleaves signal oligosaccharyltransferase adds high-mannose oligosaccharides 25 asparagine X Ser Thr motifs protein disulfide isomerase forms 8 disulfide bonds calnexin calreticulin cycle glucosidase II monitors folding peptidyl prolyl isomerase assists. Golgi further trims ma

Ref: Blood Factor VIII CHO Production Kaufman 1988; FDA Recombinant Factor VIII Manufacturing Guidelines; Alberts Protein Glycosylation Mammalian Cells Chap 15.

View Details
Gene Therapy

Hemophilia gene therapy targets deficiency of:

Hemophilia A 1 in 5000 males and B 1 in 30000 males result null mutations coagulation cofactors FVIII 280 kDa glycoprotein encoded F8 Xq28 domains A1 A2 B A3 C1 C2 and FIX vitamin K dependent serine protease encoded F9 Xq27 gamma carboxyglutamic acid residues binding calcium phospholipid. Both assemble intrinsic tenase complex FVIIIa cofactor enhancing FIXa protease activity 200000-fold toward FX activation on phosphatidylserine-rich platelet surface accelerating thrombin burst fibrin clot formation. Deficiency prolongs aPTT causing hemarthrosis, muscle hematoma. Replacement requires frequent

Ref: NEJM Hemophilia Gene Therapy Nathwani 2022; FDA Hemgenix Roctavian Approvals; Alberts Cell Biology Coagulation Cascade Chap 20.

View Details