Serveur d'exploration Chloroquine

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DC-Chol lipid system in gene transfer

Identifieur interne : 002A05 ( Main/Exploration ); précédent : 002A04; suivant : 002A06

DC-Chol lipid system in gene transfer

Auteurs : Song Li [États-Unis] ; Xiang Gao [États-Unis] ; Kyonghee Son [États-Unis] ; Frank Sorgi [États-Unis] ; Hans Hofland [États-Unis] ; Leaf Huang [États-Unis]

Source :

RBID : ISTEX:E9E618A8EAFB508D3199461CEF4D5F0BB48B3C4D

English descriptors

Abstract

Abstract: Lipidic systems including cationic liposomes offer many potential advantages for delivering functional DNA to cells in intact animals. DC-Chol:DOPE, a cationic liposome formulation developed in this laboratory, is highly efficient for delivering nucleic acids into various cell types in vitro as well as in vivo. Mixing DNA with cationic liposomes produce condensed DNA along with tubular structures and aggregated liposomes. Interaction with cell membrane, followed by endocytosis and disruption of endosomes, appears to be the main mechanism of cytoplasmic delivery of DNA by DNA/cationic liposome complex. In an attempt to overcome the low efficiency of nuclear entry of cytoplasmic DNA, a limiting step for the overall expression level of the transgene, a cytoplasmic expression system was developed. A plasmid containing the reporter gene, chloramphenicol acetyltransferase (CAT), driven by the bacteriophage T7 promoter, following co-delivery with T7 RNA polymerase by DC-Chol cationic liposomes into cells, gives a rapid, but transient CAT gene expression. However, strong and sustained gene expression could be achieved by co-delivery of a T7 RNA polymerase enzyme regenerating system such as a T7 autogene. An independent study found that a single i.p. injection of cisplatin could sensitize lipofection of tumors in situ. A combined and sequential protocol was therefore proposed for cancer gene therapy.

Url:
DOI: 10.1016/0168-3659(95)00167-0


Affiliations:


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<term>Cationic cholesterol derivatives</term>
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<term>Cationic lipids</term>
<term>Cationic liposome</term>
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<term>Cationic liposomes</term>
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<term>Cell surface</term>
<term>Cellular toxicity</term>
<term>Chloramphenicol acetyltransferase</term>
<term>Cisplatin</term>
<term>Complete regression</term>
<term>Complex formation</term>
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<term>Efficient binding</term>
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<term>Unpublished results</term>
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<div type="abstract" xml:lang="en">Abstract: Lipidic systems including cationic liposomes offer many potential advantages for delivering functional DNA to cells in intact animals. DC-Chol:DOPE, a cationic liposome formulation developed in this laboratory, is highly efficient for delivering nucleic acids into various cell types in vitro as well as in vivo. Mixing DNA with cationic liposomes produce condensed DNA along with tubular structures and aggregated liposomes. Interaction with cell membrane, followed by endocytosis and disruption of endosomes, appears to be the main mechanism of cytoplasmic delivery of DNA by DNA/cationic liposome complex. In an attempt to overcome the low efficiency of nuclear entry of cytoplasmic DNA, a limiting step for the overall expression level of the transgene, a cytoplasmic expression system was developed. A plasmid containing the reporter gene, chloramphenicol acetyltransferase (CAT), driven by the bacteriophage T7 promoter, following co-delivery with T7 RNA polymerase by DC-Chol cationic liposomes into cells, gives a rapid, but transient CAT gene expression. However, strong and sustained gene expression could be achieved by co-delivery of a T7 RNA polymerase enzyme regenerating system such as a T7 autogene. An independent study found that a single i.p. injection of cisplatin could sensitize lipofection of tumors in situ. A combined and sequential protocol was therefore proposed for cancer gene therapy.</div>
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