CAR-binding ablation does not change biodistribution and toxicity of adenoviral vectors

Non-invasive gamma camera imaging of gene transfer using an adenoviral vector encoding an epitope-tagged receptor as a reporter

“…injection of adenoviral vectors leads to high liver expression of transgenes due to the high density of the coxsackie-adenovirus receptor (CAR) present in the liver as well as other factors. 36,37 To date, many non-invasive imaging studies of gene transfer have evaluated gene expression in the liver after systemic administration of a gene delivery vehicle. Thus, the first in vivo study evaluated the liver expression of HAhSSTr2 after i.v.…”

Transductional targeting of adenovirus vectors for gene therapy

“…Strategies to inhibit hepatocyte and/or liver Kupffer cell uptake by ablating CAR-or integrin-binding motifs in the Ad capsid have been largely unsuccessful, however, indicating that native Ad tropism determinants contribute little to vector hepatotropism in vivo. [40][41][42][43][44] These data notwithstanding, work by several groups has implicated the fiber protein as a major structural determinant of liver tropism in vivo (reviewed by Nicklin et al 45 ). For example, shortening of the native fiber shaft domain of the Ad5 fiber 46 or replacement of the Ad5 shaft with the short Ad3 shaft domain 47 was shown to attenuate liver uptake in vivo following intravenous delivery.…”

Gene transfer vector biodistribution: pivotal safety studies in clinical gene therapy development

“…Other techniques include nonquantitative or semiquantitative PCR, FISH (approx. 50%), Southern blot 1,2 and reporter gene expression (LacZ, [1][2][3][4][5][6]7 luciferase, [8][9][10][11] and GFP 12 ).…”