Receptor-mediated endocytosis and nuclear transport of a transfecting DNA construct

Rosenkranz, Andrey A.; Yachmenev, S V; Jans, David A.; Serebryakova, Natalya V.; Murav'ev, Vitaly I.; Peters, Reiner; Соболев, А. С.

doi:10.1016/0014-4827(92)90441-a

Cited by 97 publications

(30 citation statements)

References 26 publications

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“…Ligand choice is largely dictated by whether or not the target receptor undergoes endocytosis. Among the additional ligands that have been tested are TGFa, 21 insulin, 22,23 folate, [24][25][26] basic FGF, 27 integrin-binding motifs, [28][29][30] and heregulin. 31 Antibodies generated against certain cell-specific receptors also have been used to direct gene transfer.…”

Section: Receptor Bindingmentioning

confidence: 99%

Intracellular trafficking of nonviral vectors

2005

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Section: Receptor Bindingmentioning

confidence: 99%

Intracellular trafficking of nonviral vectors

2005

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“…As a consequence of its polycationic character, polylysine has been used as a DNA carrier (Rosenkranz et al, 1992). Its similarity with the NLS sequence of SV40 T antigen (see above) has suggested that, in addition to acting as a gene transfer vector, it may be involved in the targeting of DNA to the cell nucleus.…”

Section: Non-covalent Association Of Dna With Nls Sequence-bearing Symentioning

confidence: 99%

Improvement of exogenous DNA nuclear importation by nuclear localization signal‐bearing vectors: a promising way for non‐viral gene therapy?

Hebert

2003

Biology of the Cell

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Several vectors have been developed in order to target genes to specific cells. Virus-based vectors lead to a high transfection efficiency in vitro, but display important disadvantages such as pathological risks, which they expose to patients. Plasmid-associated chemical vectors lack these disadvantages, but allow only a very low efficiency of transgene expression. Most of the non-viral-based gene transfer techniques developed until now mainly focused their efforts to overcome the problem of DNA entry into the cell. Some recent works, however, have begun to investigate the nucleus entry problem and suggest that the trafficking of DNA from cytosol to the nucleus may be improved by using the nuclear localization signal (NLS) found in some nuclear proteins. If the vector contains one or several NLS, either as covalently or non-covalently DNA-linked peptides, a competition may take place between the rate of dissociation of the DNA-vector complexes and the rate of loading of the complexes to the NLS-mediated nucleus importation machinery. This equilibrium may be displaced towards the importation pathway by the use of NLS-bearing proteins instead of peptides. The possibility of recruiting normal endogenous cellular pathways of nuclear uptake to promote entry of exogenously applied DNA through the nuclear pore complex would, thus, seem promising. Nevertheless, attempts to improve the transport of DNA to the nucleus through the use of NLSs have achieved limited success. Although these systems show improved transgene expression, little is known about how they function in transfected cells, and the optimal formulation for gene expression is yet to be determined.

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“…7 A number of different cationic liposomes have been developed including lipofectin, 8,9 lipofectamine, 10 DOTAP 11 and TransfectAce. 12 In receptor-mediated gene delivery, DNA is usually complexed through charge interaction to poly-l-lysine that has been cross-linked to ligands such as transferrin, 13 asialoglycoprotein, 14 mannose 15 or insulin, 16 which confer both cell specificity and receptor-mediated internalization. Multidomain recombinant chimeric proteins as well as peptide-protein conjugates [17][18][19] have also been used as an alternative in which one domain or peptide in the chimeric protein enables it to target specific cells, while another acts as a carrier for DNA uptake via receptor-mediated endocytosis.…”

Section: Introductionmentioning

confidence: 99%

Mutual exclusivity of DNA binding and nuclear localization signal recognition by the yeast transcription factor GAL4: implications for nonviral DNA delivery

et al. 1998

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A novel approach to nonviral DNA delivery is the use of ties of GAL4. We demonstrate that GAL4(1-147) can combinations of DNA-binding proteins such as the yeast specifically enhance transfection of plasmids containing transcriptional activator GAL4 and plasmid DNA containing the 17 bp recognition sequence. Interestingly, we found the specific binding sequence of the DNA-binding protein that the nuclear localization signal (NLS) of GAL4 is distinct inserted within it, in addition to the gene of interest to be from conventional NLSs, such as those of the SV40 large transferred into target cells. The amino terminal 147 amino tumor antigen and bipartite NLSs, in that it is recognized acids of GAL4 contain a DNA-binding domain that has exclusively by the nuclear pore targeting ␤-subunit of the been shown to bind specifically to a 17 bp nucleotide rec-NLS-receptor importin complex, rather than the ␣-subunit. ognition sequence, while the amino terminal 74 amino Specific binding to DNA was blocked by ␤-subunit binding, acids have been shown to be sufficient to target large hetwhile the converse was also true, making the GAL4-NLS erologous proteins to the nucleus. Although it has been novel in being regulated by DNA binding; this may play an previously exploited as a gene transfer vehicle, the exact important role in effecting release of GAL4 from the ␤-subrelationship between GAL4's DNA binding and nuclear tarunit following transport through the nuclear pore. This geting activities has not been investigated. Using gel study encompasses the first direct analysis of NLS mobility shift assays and ELISA-based binding assays, this recognition/accessibility in vehicles for nonviral DNA transstudy examines this issue directly, establishing the mutual fer, with the results having relevance to the use of GAL4 exclusivity of the DNA-binding and nuclear targeting activiand comparable DNA-binding proteins in such vehicles.

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Receptor-mediated endocytosis and nuclear transport of a transfecting DNA construct

Cited by 97 publications

References 26 publications

Intracellular trafficking of nonviral vectors

Intracellular trafficking of nonviral vectors

Improvement of exogenous DNA nuclear importation by nuclear localization signal‐bearing vectors: a promising way for non‐viral gene therapy?

Mutual exclusivity of DNA binding and nuclear localization signal recognition by the yeast transcription factor GAL4: implications for nonviral DNA delivery

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