Inflammation Promotes the Loss of Adeno-associated Virus-mediated Transgene Expression in Mouse Liver

Overview

Journal Gastroenterology

Specialty Gastroenterology

Date 2011 Jun 7

PMID 21640112

Citations 21

Authors

Ekaterina Breous

Suryanarayan Somanathan

Peter Bell

James M Wilson

Affiliations

Soon will be listed here.

Abstract

Background & Aims: Non-self transgenes delivered to mouse liver via adeno-associated virus (AAV) are expressed stably due to the induction of immune tolerance. However, such transgene expression has been reported to be lost in higher-order primates. We investigated whether inflammatory processes, which likely differ between species, impact the stability of transgene expression.

Methods: We developed a mouse model that mimics a scenario in which a subject that has received hepatic AAV-mediated gene transfer develops subsequent, vector-unrelated, systemic inflammation.

Results: Inflammation eliminated previously stable expression of transgenes delivered by AAV; the limited tissue destruction and persistence of AAV genomes implicated pathways besides the cytotoxic T-cell response. Tumor necrosis factor-a down-regulated expression of the transgene from the AAV, indicating a role for similar inflammatory cytokines in such loss of transgene expression.

Conclusions: Inflammation can block AAV-mediated expression of transgenes in mouse liver. The presence of inflammation might therefore affect hepatic expression of transgenes from viral vectors in humans.

Citing Articles

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