Use of protamine to augment adenovirus-mediated cancer gene therapy

Trans-complementation of vector replication versus Coxsackie-adenovirus-receptor overexpression to improve transgene expression in poorly permissive cancer cells

“…Mean fluorescent intensity (MFI) was used as a semiquantitative measure of the number of adenovirus receptor molecules per cell. 21 In order to determine which of the receptors limits AdV uptake, we analyzed the correlations between MFI values and the number of AdV genomic DNA copies in each infected cell line (Table 1) using Pearson's product moment. Only CAR expression correlated significantly with the number of AdV DNA copies in the infected cells (r = 0.68; P Ͻ 0.05), whereas there was no correlation with ␣ v ␤ 3 or ␣ v ␤ 5 integrins.…”

“…Almost complete resistance against AdV-mediated gene transfer in human glioma, 15 human bladder cancer 14 and human melanoma cells 16 was correlated with low CAR expression, while no association was observed to ␣ v ␤ 3 -and ␣ v ␤ 5 -integrin expression. Approaches to improve the gene transfer rate include fiber knob domain modifications [17][18][19][20] or the addition of polycations 21 in order to achieve CAR-independent gene transfer, and overexpression of CAR. 12,13,22 The latter has been reported to increase vector uptake up to 1000-fold in primarily resistant cells such as human dermal fibroblasts.…”

Branched oligomerization of cell-permeable peptides markedly enhances the transduction efficiency of adenovirus into mesenchymal stem cells

“…First, cationic polymers and lipids, which form complexes with adenoviral particles, have been used to facilitate in vitro transduction of a range of cell types by rAd. 29,30 In fact, although protamine sulfate, which is one of the well-known cationic polymer, increased rAd delivery into several cell lines and primary cells, lower transduction efficiency (B70%) was shown in MSCs (Supplementary Table 1). On the other hand, high molecular weight poly-L-lysine, polybrene, DEAEDextran and lipofectamine showed similar transduction efficiency (490%) of MSCs by rAd compared with tetrameric CPPs.…”

Development of formulations that enhance physical stability of viral vectors for gene therapy

“…6,7 To date, most formulation efforts reported in the literature are focused on the addition of excipients to vector preparations to enhance transduction efficiency in vivo. [8][9][10][11] Few reports describe the physical stability of viral vectors for gene therapy. 12,13 This report is the first to summarize efforts to systematically develop formulations that enhance the physical and chemical stability of viral vectors at ambient temperature.…”