J. Huard et al., THE ROUTE OF ADMINISTRATION IS A MAJOR DETERMINANT OF THE TRANSDUCTION EFFICIENCY OF RAT-TISSUES BY ADENOVIRAL RECOMBINANTS, Gene therapy, 2(2), 1995, pp. 107-115
One of the key factors that determines the efficacy of adenovirus-medi
ated gene therapy in genetic diseases, is the degree and extent of tra
nsduction of the target cells by adenovirus (AV)-recombinants carrying
the therapeutic gene or cDNA. In this paper we provide experimental e
vidence which indicates that the route of administration of the AV-rec
ombinants has a major influence on the transduction of various tissues
in young rats. The heart, diaphragm, intercostal muscles and thymus s
how high transduction after intra-arterial (left cardiac ventricle) in
jection. By contrast, the liver shows a high transduction after intrav
enous injection. A substantial viremia develops within 2 h of gastric-
rectal, intraperitoneal and intracardiac administration of AV recombin
ants. The number of adenoviral DNA copies per nucleus of transduced ce
lls ranged from one to three in most tissues. These numbers correlated
well with the overall transduction efficiency of the tissue determine
d by reporter gene expression. The various factors that determine whic
h route of administration favors a high transduction rate in a particu
lar tissue can be analyzed and this can lead to an improved efficiency
of gene therapy in targeting a particular tissue in a disease.