The relevance of coagulation factor X protection of adenoviruses in human sera.

Abstract:

:Intravenous delivery of adenoviruses is the optimal route for many gene therapy applications. Once in the blood, coagulation factor X (FX) binds to the adenovirus capsid and protects the virion from natural antibody and classical complement-mediated neutralisation in mice. However, to date, no studies have examined the relevance of this FX/viral immune protective mechanism in human samples. In this study, we assessed the effects of blocking FX on adenovirus type 5 (Ad5) activity in the presence of human serum. FX prevented human IgM binding directly to the virus. In individual human sera samples (n=25), approximately half of those screened inhibited adenovirus transduction only when the Ad5-FX interaction was blocked, demonstrating that FX protected the virus from neutralising components in a large proportion of human sera. In contrast, the remainder of sera tested had no inhibitory effects on Ad5 transduction and FX armament was not required for effective gene transfer. In human sera in which FX had a protective role, Ad5 induced lower levels of complement activation in the presence of FX. We therefore demonstrate for the first time the importance of Ad-FX protection in human samples and highlight subject variability and species-specific differences as key considerations for adenoviral gene therapy.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Duffy MR,Doszpoly A,Turner G,Nicklin SA,Baker AH

doi

10.1038/gt.2016.32

subject

Has Abstract

pub_date

2016-07-01 00:00:00

pages

592-6

issue

7

eissn

0969-7128

issn

1476-5462

pii

gt201632

journal_volume

23

pub_type

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