Unknown

Dataset Information

0

Biodistribution and retargeting of FX-binding ablated adenovirus serotype 5 vectors.


ABSTRACT: A 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.

SUBMITTER: Alba R 

PROVIDER: S-EPMC2974579 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications


A 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,  ...[more]

Similar Datasets

| S-EPMC2721791 | biostudies-literature
| S-EPMC8519182 | biostudies-literature
| S-EPMC2584667 | biostudies-literature
2016-06-01 | GSE73118 | GEO
| S-EPMC4810268 | biostudies-literature
2016-06-01 | E-GEOD-73118 | biostudies-arrayexpress
| S-EPMC5288196 | biostudies-literature
| S-EPMC3060954 | biostudies-literature
| S-EPMC1900173 | biostudies-literature
| S-EPMC2169084 | biostudies-literature