scholarly journals Prevalence and pharmacological modulation of humoral immunity to AAV vectors in gene transfer to synovial tissue

Gene Therapy ◽  
2012 ◽  
Vol 20 (4) ◽  
pp. 417-424 ◽  
Author(s):  
F Mingozzi ◽  
Y Chen ◽  
S C Edmonson ◽  
S Zhou ◽  
R M Thurlings ◽  
...  
2012 ◽  
Vol 20 (7) ◽  
pp. 1410-1416 ◽  
Author(s):  
Federico Mingozzi ◽  
Yifeng Chen ◽  
Samuel L Murphy ◽  
Shyrie C Edmonson ◽  
Alex Tai ◽  
...  

Gene Therapy ◽  
2011 ◽  
Vol 19 (1) ◽  
pp. 78-85 ◽  
Author(s):  
J H McIntosh ◽  
M Cochrane ◽  
S Cobbold ◽  
H Waldmann ◽  
S A Nathwani ◽  
...  

1997 ◽  
Vol 56 ◽  
pp. 38
Author(s):  
Paulien Goossens ◽  
Bram Bout ◽  
Bert 't Hart ◽  
Els Kindell ◽  
Ferdinand Breedveld ◽  
...  

1999 ◽  
Vol 73 (8) ◽  
pp. 6930-6936 ◽  
Author(s):  
Christian Hofmann ◽  
Peter Löser ◽  
Günter Cichon ◽  
Wolfgang Arnold ◽  
Gerald W. Both ◽  
...  

ABSTRACT Recombinant human adenoviruses (hAd) have become widely used as tools to achieve efficient gene transfer. However, successful application of hAd-derived vectors in clinical trials is limited due to immunological and potential safety problems inherent in their human origin. In this study, we describe a recombinant ovine adenovirus (OAV) as an alternative vector for gene transfer in vivo. In contrast to an hAd vector, the OAV vector was not neutralized by human sera. An OAV vector which contained the cDNA of the human α1-antitrypsin (hAAT) gene linked to the Rous sarcoma virus promoter was generated and administered systemically to mice. The level and duration of hAAT gene expression was similar to that achieved with an hAd counterpart in both immunocompetent and immunodeficient mice. However, the tissue distribution of the OAV vector differed from that observed for hAd vectors in that the liver was not the dominant target. Significantly, we demonstrated efficient gene transfer with the OAV vector into mice immunized with hAd vectors and vice versa. We also confirm that the immune response to a transgene product can prevent its functional expression following sequential application of a vector. Our results suggest a possible solution to endemic humoral immunity against currently used hAd vectors and should therefore have an impact on the design of improved gene therapy protocols utilizing adenovirus vectors.


2017 ◽  
Vol 1 (23) ◽  
pp. 2019-2031 ◽  
Author(s):  
Amine Meliani ◽  
Florence Boisgerault ◽  
Zachary Fitzpatrick ◽  
Solenne Marmier ◽  
Christian Leborgne ◽  
...  

Key Points Enveloped AAV vectors are able to transduce the liver highly efficiently, driving superior correction of hemophilia B in mice. Enveloped AAVs are less susceptible to antibody-mediated neutralization, allowing for liver transduction in preimmunized animals.


2001 ◽  
Vol 44 (1) ◽  
pp. 48-52 ◽  
Author(s):  
Paulien H. Goossens ◽  
Ronald Vogels ◽  
Elsbet Pieterman ◽  
Menzo J. E. Havenga ◽  
Abraham Bout ◽  
...  

Author(s):  
S. Laoussadi ◽  
A. Kahan ◽  
G. Aubouy ◽  
F. Delbarre

Several patients with Fabry's, Gaucher's diseases and hyperlipoproteinemia type II and with arthropatic manifestations were observed.As no histological explanation for these symptoms was available,an ultrastructural study of synovial tissue was done to establish an anatomoclinical relation.Material and Methods :synovial membrane samples were obtained by needle biopsies of the knee from three patients with arthropatic manifestations of each disease.They were fixed in 5% glutaraldehyde, postfixed in 1% osmium tetraoxyde and embedded in Epon 812. Thin sections coloured by uranyl acetate and lead citrate were observed with an Elmiskop I Siemens electron microscope.Two important phenomena were observed in synovial tissue:Specific patterns of each lipid storage disease,which are now well known.In all the three metabolic diseases, hydroxyapatite-like crystals were found. They are characterized by their intramitochondrial localization, without any relation with cristae,an anarchic disposition and a mean size of 550 A.Crystals may be found also free in the cytoplasm of synoviocytes Some micrographs suggest an evolution in four steps :a. mitochondria with only a few microcrystalsb. mitochondria stuffed with these structuresc. disruption of mitochondria membranesd. microcrystals appear free in the cytoplasm


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