A mouse model for adenovirus gene delivery

doi:10.1073/pnas.141223398

A mouse model for adenovirus gene delivery

^*Center for Genomics Research, ^†Institute for Cell and Molecular Biology, ^‡Cancer Centrum Karolinska, Karolinska Institutet, 171-77 Stockholm, Sweden

Contributed by Lennart Philipson

Abstract

The cellular attachment receptor for adenovirus (Ad), Coxsackie adenovirus receptor (CAR), required for delivery of Ad into primary cells, is not present on all cell types, thus restricting Ad-gene delivery systems. To circumvent this constrain, a transgenic mouse has been generated that expresses a truncated human CAR in all tissues analyzed. These mice allowed efficient in vitro infections at low multiplicities into lymphoid, myeloid, and endothelial cells. Furthermore, in vivo administration of Ad-vectors results in infection of macrophages, lymphocytes, and endothelial cells. In addition, tail vein injection resulted in targeting of virus into previously inaccessible areas, such as the lung and the capillaries of the brain. The CAR transgenic mice will be useful for rapid functional genomic analysis in vivo, for testing the efficacy of gene therapy procedures or as a source of easily transducible cells.

Footnotes

↵ § To whom reprint requests should be addressed. E-mail: sven.pettersson{at}cgr.ki.se.
Abbreviations:

Ad,

adenovirus;

CAR,

Coxsackie and adenovirus receptor;

PMA,

phorbol 12-myristate 13-acetate;

DCs,

dendritic cells;

AdGFP,

recombinant Ad vmAdCG;

AdLacZ,

recombinant Ad pTG-Z;

PE,

phycoerythrin;

hCAR,

human CAR;

GFP,

green fluorescent protein;

MOI,

multiplicity of infection