Bacterial Virus Gene Expression in Human Cells

Merril, Carl R.; Geier, Mark R.; Petricciani, John C.

doi:10.1038/233398a0

Cited by 197 publications

(71 citation statements)

References 19 publications

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“…For example, a galactose transferase gene incorporated into the phage lambda genome could be expressed as mRNA and translated as protein in human fibroblast cells exposed to the viable phage or phage DNA (Geier & Merril, 1972;Merril et al, 1971). However, there is no indication that the complex series of processes involved in reproducing phage T4 could be carried out in a eukaryotic cell, where the whole machinery and regulatory mechanisms are very different from those in bacteria.…”

Section: Safety Issuesmentioning

confidence: 99%

Phage therapy: the Escherichia coli experience

2005

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Phages have been proposed as natural antimicrobial agents to fight bacterial infections in humans, in animals or in crops of agricultural importance. Phages have also been discussed as hygiene measures in food production facilities and hospitals. These proposals have a long history, but are currently going through a kind of renaissance as documented by a spate of recent reviews. This review discusses the potential of phage therapy with a specific example, namely Escherichia coli.

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Section: Safety Issuesmentioning

confidence: 99%

Phage therapy: the Escherichia coli experience

2005

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“…No decrease in the protein expression was achieved with these formulations or with the lipoplexes without CPP, although a decrease in survivin mRNA levels has been observed for the ternary complexes in both A549 and HeLa cells ( Figure 6B). Since the 1970s, when gene therapy was first described, 36 great efforts have been expended toward the discovery of appropriate delivery systems able to surpass the cell membrane and release the different types of nucleic acid molecules, ranging from long DNA molecules to small double-stranded siRNAs, into the target intracellular compartment. Despite the recent advances concerning plasmid DNA and siRNA delivery to target cells, further work should be developed to achieve high levels of cellular uptake and long-term stability, while avoiding unspecific effects, so that nucleic acid therapeutics can reach their full potential as a clinically relevant option.…”

Section: Molecular Pharmaceuticsmentioning

confidence: 99%

Comparison of the Efficiency of Complexes Based on S4₁₃-PV Cell-Penetrating Peptides in Plasmid DNA and siRNA Delivery

et al. 2013

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The successful application of gene therapy approaches is highly dependent on the efficient delivery of nucleic acids into target cells. In the present study, new peptide-based nonviral systems were developed to enhance plasmid DNA and siRNA delivery, aiming at generating appropriate gene delivery and gene silencing tools for preclinical and clinical application. For this purpose, a new cell-penetrating peptide derived from the wild-type S4 13 -PV peptide was synthesized through the addition of a five-histidine tail to its N-terminus (H 5 -S4 13 -PV), and its ability to mediate gene expression and gene silencing was evaluated and compared to that of the wild-type peptide. The histidine-enriched peptide, H 5 -S4 13 -PV, proved to be generally more efficient and less toxic than the wild-type peptide in the delivery of plasmid DNA. In addition, complexes of H 5 -S4 13 -PV with siRNAs, but not of S4 13 -PV, were efficiently internalized by cells and presented high knockdown activity (63%). Interestingly, systems containing the S4 13 -PV or the H 5 -S4 13 -PV peptide exhibited superior biological activity when compared to those containing the reverse NLS or scrambled peptides, suggesting that both the cell-penetrating sequence and the NLS of the S4 13 -PV peptide influence the competence of binary and ternary complexes to accomplish nucleic acid delivery. In order to unravel the cancer therapeutic potential of formulations with the histidine-enriched peptide, their efficiency to mediate silencing of the oncogenic protein survivin was evaluated. As opposed to complexes with the wild-type peptide, H 5 -S4 13 -PV complexes showed the ability to promote a high survivin knockdown at the level of both protein (44%) and mRNA (73%), in HT1080 cells.

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“…But Merrill, Geier and Petricciani induced human cells to initiate enzyme synthesis through infectious (bacterial) gene change (33)…”

Section: Smoke Screensmentioning

confidence: 99%