scholarly journals Development of a Novel Fully Functional Coagulation Factor VIII with Reduced Immunogenicity Utilizing an In silico Prediction and Deimmunization Approach

2021 ◽  
Author(s):  
Karina Winterling ◽  
William D. Martin ◽  
Anne S. De Groot ◽  
Jens Daufenbach ◽  
Steffen Kistner ◽  
...  
Keyword(s):  
Factor Viii ◽  
In Silico ◽  
Coagulation Factor ◽  
Coagulation Factor Viii ◽  
In Silico Prediction

scholarly journals Generation of active coagulation factor VIII from isolated subunits.

1988 ◽  
Vol 263 (3) ◽  
pp. 1115-1118
Author(s):  
O Nordfang ◽  
M Ezban
Keyword(s):  
Factor Viii ◽  
Coagulation Factor ◽  
Coagulation Factor Viii

scholarly journals Inhibition of human coagulation factor VIII by monoclonal antibodies. Mapping of functional epitopes with the use of recombinant factor VIII fragments

1989 ◽  
Vol 263 (1) ◽  
pp. 187-194 ◽  
Author(s):  
A Leyte ◽  
K Mertens ◽  
B Distel ◽  
R F Evers ◽  
M J M De Keyzer-Nellen ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Factor Viii ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Procoagulant Activity ◽  
Coagulation Factor Viii ◽  
Coagulation Cascade ◽  
Restriction Enzyme Digestion ◽  
Proteolytic Activation

The epitopes of four monoclonal antibodies against coagulation Factor VIII were mapped with the use of recombinant DNA techniques. Full-length Factor VIII cDNA and parts thereof were inserted into the vector pSP64, permitting transcription in vitro with the use of a promoter specific for SP6 RNA polymerase. Factor VIII DNA inserts were truncated from their 3′-ends by selective restriction-enzyme digestion and used as templates for ‘run-off’ mRNA synthesis. Translation in vitro with rabbit reticulocyte lysate provided defined radiolabelled Factor VIII fragments for immunoprecipitation studies. Two antibodies are shown to be directed against epitopes on the 90 kDa chain of Factor VIII, between residues 712 and 741. The 80 kDa chain appeared to contain the epitopes of the other two antibodies, within the sequences 1649-1778 and 1779-1840 respectively. The effect of antibody binding to these sequences was evaluated at two distinct levels within the coagulation cascade. Both Factor VIII procoagulant activity and Factor VIII cofactor function in Factor Xa generation were neutralized upon binding to the region 1779-1840. The antibodies recognizing the region 713-740 or 1649-1778, though interfering with Factor VIII procoagulant activity, did not inhibit in Factor Xa generation. These findings demonstrate that antibodies that virtually inhibit Factor VIII in coagulation in vitro are not necessarily directed against epitopes involved in Factor VIII cofactor function. Inhibition of procoagulant activity rather than of cofactor function itself may be explained by interference in proteolytic activation of Factor VIII. This hypothesis is in agreement with the localization of the epitopes in the proximity of thrombin-cleavage or Factor Xa-cleavage sites.

scholarly journals Characterization and visualization of murine coagulation factor VIII-producing cells in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Morisada Hayakawa ◽  
Asuka Sakata ◽  
Hiroko Hayakawa ◽  
Hikari Matsumoto ◽  
Takafumi Hiramoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Factor Viii ◽  
Fluorescent Protein ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Genetically Engineered ◽  
Coagulation Factor Viii ◽  
Liver Sinusoidal Endothelial Cells ◽  
Genetically Engineered Mice

AbstractCoagulation factors are produced from hepatocytes, whereas production of coagulation factor VIII (FVIII) from primary tissues and cell species is still controversial. Here, we tried to characterize primary FVIII-producing organ and cell species using genetically engineered mice, in which enhanced green fluorescent protein (EGFP) was expressed instead of the F8 gene. EGFP-positive FVIII-producing cells existed only in thin sinusoidal layer of the liver and characterized as CD31high, CD146high, and lymphatic vascular endothelial hyaluronan receptor 1 (Lyve1)+. EGFP-positive cells can be clearly distinguished from lymphatic endothelial cells in the expression profile of the podoplanin− and C-type lectin-like receptor-2 (CLEC-2)+. In embryogenesis, EGFP-positive cells began to emerge at E14.5 and subsequently increased according to liver maturation. Furthermore, plasma FVIII could be abolished by crossing F8 conditional deficient mice with Lyve1-Cre mice. In conclusion, in mice, FVIII is only produced from endothelial cells exhibiting CD31high, CD146high, Lyve1+, CLEC-2+, and podoplanin− in liver sinusoidal endothelial cells.

scholarly journals Patient preference and ease of use for different coagulation factor VIII reconstitution device scenarios: a cross-sectional survey in five European countries

2014 ◽  
pp. 1713 ◽  
Author(s):  
Ernesto Cimino ◽  
Silvia Linari ◽  
Mara Malerba ◽  
Susan Halimeh ◽  
Francesca Biondo ◽  
...  
Keyword(s):  
Factor Viii ◽  
Patient Preference ◽  
Coagulation Factor ◽  
Ease Of Use ◽  
European Countries ◽  
Coagulation Factor Viii ◽  
Cross Sectional Survey ◽  
Cross Sectional

Molecular genetics of coagulation factor VIII gene and haemophilia A

Haemophilia ◽  
1998 ◽  
Vol 4 (s2) ◽  
pp. 1-11 ◽  
Author(s):  
S. E. Antonarakis
Keyword(s):  
Factor Viii ◽  
Molecular Genetics ◽  
Coagulation Factor ◽  
Coagulation Factor Viii ◽  
Haemophilia A ◽  
Factor Viii Gene

A Limited Sampling Strategy for Estimating Individual Pharmacokinetic Parameters of Coagulation Factor VIII in Patients With Hemophilia A

2007 ◽  
Vol 29 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Magali Bolon-Larger ◽  
Val??rie Chamouard ◽  
Fran??oise Bressolle ◽  
Roselyne Boulieu
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Coagulation Factor ◽  
Sampling Strategy ◽  
Limited Sampling Strategy ◽  
Coagulation Factor Viii ◽  
Pharmacokinetic Parameters ◽  
Limited Sampling
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