Biological barriers to cellular delivery of lipid-based DNA carriers
Identifieur interne : 001322 ( Istex/Checkpoint ); précédent : 001321; suivant : 001323Biological barriers to cellular delivery of lipid-based DNA carriers
Auteurs : Marcel B. Bally [Canada] ; Pierrot Harvie [Canada] ; Frances M. P Wong [Canada] ; Spencer Kong [Canada] ; Ellen K. Wasan [Canada] ; Dorothy L. Reimer [Canada]Source :
- Advanced Drug Delivery Reviews [ 0169-409X ] ; 1999.
Abstract
Although lipid-based DNA delivery systems are being assessed in gene therapy clinical trials, many investigators in this field are concerned about the inefficiency of lipid-based gene transfer technology, a criticism directed at all formulations used to enhance transfer of plasmid expression vectors. It is important to recognize that many approaches have been taken to improve transfection efficiency, however because of the complex nature of the formulation technology being developed, it has been extremely difficult to define specific carrier attributes that enhance transfection. We believe that these optimization processes are flawed for two reasons. First, a very defined change in formulation components affects the physical and chemical characteristics of the carrier in many ways. As a consequence, it has not been possible to define structure/activity relationships. Second, the primary endpoint used to assess plasmid delivery has been transgene expression, an activity that is under the control of cellular processes that have nothing to do with delivery. Gene expression following administration of a plasmid expression vector involves a number of critical steps: (i) DNA protection, (ii) binding to a specific cell population, (iii) DNA transfer across the cell membrane, (iv) release of DNA into the cytoplasm, (v) transport through the cell and across the nuclear membrane as well as (vi) transcription and translation of the gene. The objective of this review is to describe lipid-based DNA carrier systems and the attributes believed to be important in regulating the transfection activity of these formulations. Although membrane destabilization activity of the lipid-based carriers plays an important role, we suggest here that a critical element required for efficient transfection is dissociation of lipids bound to the plasmid expression vector following internalization.
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DOI: 10.1016/S0169-409X(99)00034-4
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Reimer</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Medical Oncology–Advanced Therapeutics, British Columbia Cancer Agency and Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6</wicri:regionArea><wicri:noRegion>British Columbia V5Z 4E6</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Advanced Drug Delivery Reviews</title><title level="j" type="abbrev">ADR</title><idno type="ISSN">0169-409X</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1999">1999</date><biblScope unit="volume">38</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="291">291</biblScope><biblScope unit="page" to="315">315</biblScope></imprint><idno type="ISSN">0169-409X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0169-409X</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Although lipid-based DNA delivery systems are being assessed in gene therapy clinical trials, many investigators in this field are concerned about the inefficiency of lipid-based gene transfer technology, a criticism directed at all formulations used to enhance transfer of plasmid expression vectors. It is important to recognize that many approaches have been taken to improve transfection efficiency, however because of the complex nature of the formulation technology being developed, it has been extremely difficult to define specific carrier attributes that enhance transfection. We believe that these optimization processes are flawed for two reasons. First, a very defined change in formulation components affects the physical and chemical characteristics of the carrier in many ways. As a consequence, it has not been possible to define structure/activity relationships. Second, the primary endpoint used to assess plasmid delivery has been transgene expression, an activity that is under the control of cellular processes that have nothing to do with delivery. Gene expression following administration of a plasmid expression vector involves a number of critical steps: (i) DNA protection, (ii) binding to a specific cell population, (iii) DNA transfer across the cell membrane, (iv) release of DNA into the cytoplasm, (v) transport through the cell and across the nuclear membrane as well as (vi) transcription and translation of the gene. The objective of this review is to describe lipid-based DNA carrier systems and the attributes believed to be important in regulating the transfection activity of these formulations. Although membrane destabilization activity of the lipid-based carriers plays an important role, we suggest here that a critical element required for efficient transfection is dissociation of lipids bound to the plasmid expression vector following internalization.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Bally, Marcel B" sort="Bally, Marcel B" uniqKey="Bally M" first="Marcel B" last="Bally">Marcel B. Bally</name></noRegion><name sortKey="Bally, Marcel B" sort="Bally, Marcel B" uniqKey="Bally M" first="Marcel B" last="Bally">Marcel B. Bally</name><name sortKey="Harvie, Pierrot" sort="Harvie, Pierrot" uniqKey="Harvie P" first="Pierrot" last="Harvie">Pierrot Harvie</name><name sortKey="Kong, Spencer" sort="Kong, Spencer" uniqKey="Kong S" first="Spencer" last="Kong">Spencer Kong</name><name sortKey="Reimer, Dorothy L" sort="Reimer, Dorothy L" uniqKey="Reimer D" first="Dorothy L" last="Reimer">Dorothy L. Reimer</name><name sortKey="Wasan, Ellen K" sort="Wasan, Ellen K" uniqKey="Wasan E" first="Ellen K" last="Wasan">Ellen K. Wasan</name><name sortKey="Wong, Frances M P" sort="Wong, Frances M P" uniqKey="Wong F" first="Frances M. P" last="Wong">Frances M. P Wong</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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