scholarly journals Influence of Coagulation Factor X on In Vitro and In Vivo Gene Delivery by Adenovirus (Ad) 5, Ad35, and Chimeric Ad5/Ad35 Vectors

2009 ◽  
Vol 17 (10) ◽  
pp. 1683-1691 ◽  
Author(s):  
Jenny A Greig ◽  
Suzanne MK Buckley ◽  
Simon N Waddington ◽  
Alan L Parker ◽  
David Bhella ◽  
...  
FEBS Letters ◽  
2001 ◽  
Vol 504 (3) ◽  
pp. 99-103 ◽  
Author(s):  
Kenneth Lundstrom ◽  
Christophe Schweitzer ◽  
Daniel Rotmann ◽  
Danielle Hermann ◽  
Edith M. Schneider ◽  
...  

2015 ◽  
Vol 11 (2) ◽  
pp. e1004673 ◽  
Author(s):  
Jiangtao Ma ◽  
Margaret R. Duffy ◽  
Lin Deng ◽  
Rachel S. Dakin ◽  
Taco Uil ◽  
...  

2016 ◽  
Vol 27 (3) ◽  
pp. 549-561 ◽  
Author(s):  
M. Dolores Giron-Gonzalez ◽  
Rafael Salto-Gonzalez ◽  
F. Javier Lopez-Jaramillo ◽  
Alfonso Salinas-Castillo ◽  
Ana Belen Jodar-Reyes ◽  
...  

2016 ◽  
Vol 55 (39) ◽  
pp. 12013-12017 ◽  
Author(s):  
Yilong Cheng ◽  
Roma C. Yumul ◽  
Suzie H. Pun

Blood ◽  
2020 ◽  
Author(s):  
Georg Obermayer ◽  
Taras Afonyushkin ◽  
Laura Goederle ◽  
Florian Puhm ◽  
Waltraud C. Schrottmaier ◽  
...  

Thrombosis and the complications associated with it are a major cause of morbidity and mortality worldwide. Microvesicles (MVs), a class of extracellular vesicles, are increasingly recognized as mediators of coagulation and biomarkers of thrombotic risk. Thus, identifying factors targeting MV-driven coagulation may help in the development of novel antithrombotic treatments. We have previously identified a subset of circulating MVs that is characterized by the presence of oxidation-specific epitopes and bound by natural IgM antibodies targeting these structures. Here, we investigated whether natural IgM antibodies, which are known to have important anti-inflammatory house-keeping functions, inhibit the procoagulatory properties of MVs. We found that the extent of plasma coagulation is inversely associated with the levels of both free and MV-bound endogenous IgM. Moreover, the oxidation epitope-specific natural IgM antibody LR04, which recognizes malondialdehyde adducts, reduced MV-dependent plasmatic coagulation and whole blood clotting without affecting thrombocyte aggregation. Intravenous injection of LR04 protected mice from MV-induced pulmonary thrombosis. Of note, LR04 competed the binding of coagulation factor X/Xa to MVs, providing a mechanistic explanation for its anticoagulatory effect. Thus, our data identify natural IgM antibodies as hitherto unknown modulators of MV-induced coagulation in vitro and in vivo and their prognostic and therapeutic potential in the management of thrombosis.


2017 ◽  
Vol 5 (24) ◽  
pp. 4732-4744 ◽  
Author(s):  
A. Venault ◽  
Y.-C. Huang ◽  
J. W. Lo ◽  
C.-J. Chou ◽  
A. Chinnathambi ◽  
...  

Although PEGylated polyplexes for gene delivery are widespread, there is a need for an in-depth investigation of the role of the PEGylation degree on the delivery efficiency of the systems.


PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e47159 ◽  
Author(s):  
Hong-Sheng Wang ◽  
Zhuo-Jia Chen ◽  
Ge Zhang ◽  
Xue-Ling Ou ◽  
Xiang-Ling Yang ◽  
...  

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2656-2664 ◽  
Author(s):  
Raul Alba ◽  
Angela C. Bradshaw ◽  
Lynda Coughlan ◽  
Laura Denby ◽  
Robert A. McDonald ◽  
...  

AbstractA major limitation for adenoviral transduction in vivo is the profound liver tropism of adenovirus type 5 (Ad5). Recently, we demonstrated that coagulation factor X (FX) binds to Ad5-hexon protein at high affinity to mediate hepatocyte transduction after intravascular delivery. We developed novel genetically FX-binding ablated Ad5 vectors with lower liver transduction. Here, we demonstrate that FX-binding ablated Ad5 predominantly localize to the liver and spleen 1 hour after injection; however, they had highly reduced liver transduction in both control and macrophage-depleted mice compared with Ad5. At high doses in macrophage-depleted mice, FX-binding ablated vectors transduced the spleen more efficiently than Ad5. Immunohistochemical studies demonstrated transgene colocalization with CD11c+, ER-TR7+, and MAdCAM-1+ cells in the splenic marginal zone. Systemic inflammatory profiles were broadly similar between FX-binding ablated Ad5 and Ad5 at low and intermediate doses, although higher levels of several inflammatory proteins were observed at the highest dose of FX-binding ablated Ad5. Subsequently, we generated a FX-binding ablated virus containing a high affinity Ad35 fiber that mediated a significant improvement in lung/liver ratio in macrophage-depleted CD46+ mice compared with controls. Therefore, this study documents the biodistribution and reports the retargeting capacity of FX binding-ablated Ad5 vectors in vitro and in vivo.


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