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An apoE-peptide carrier delivers antisense DNA into cell nuclei, cutting CETP mRNA over 50% and CETP activity to 53.8% of control in CHO cells (Arterioscler Thromb Vasc Biol 1999)
Original title: Efficient nuclear delivery of antisense oligodeoxynucleotides and selective inhibition of CETP expression by apo E peptide in a human CETP-stably transfected CHO cell line
To develop a new approach for regulating CETP expression, the authors used the synthetic peptide carrier N,N-dipalmitylglycyl-apolipoprotein E (129-169) (dpGapoE) to deliver phosphorothioate antisense oligodeoxynucleotides against human CETP cDNA into a CETP-stably transfected Chinese hamster ovary (CHO) cell line. More than 95% of cells showed nuclear translocation of the oligodeoxynucleotides by 6 to 12 hours, with no membrane disruption. Cellular CETP mRNA declined, reaching a maximum reduction of more than 50% at 36 hours before recovering, while CETP activity in the culture medium declined to a maximum reduction of 53.8% of control at 36 hours. Neither CETP mRNA nor activity changed after transfection of sense oligodeoxynucleotides or naked antisense oligodeoxynucleotides. The authors conclude dpGapoE is an effective, nontoxic vehicle for nuclear antisense delivery that selectively inhibits CETP expression and activity.
Original abstract
N,N-Dipalmitylglycyl-apolipoprotein E (129-169) peptide (dpGapoE) is an efficient gene delivery system for both plasmids and antisense oligodeoxynucleotides (ODNs). To develop a new and efficient approach to the regulation of cholesteryl ester transfer protein (CETP) expression, we used dpGapoE to transfect phosphorothioate antisense ODNs against nucleotides 329 to 349 of human CETP cDNA into a human CETP-stably transfected Chinese hamster ovary (CHO) cell line (hCETP-CHO). After transfection, translocation to the nuclei and concentration in nuclear structures were observed in >95% of the cells at 6 and 12 hours by fluorescence microscopy. No membrane disruption was observed after transfection of ODNs by dpGapoE. Although the translocation stability of phosphorothioate ODNs in the nuclei continued for >48 hours, it had weakened after 24 hours. Cellular CETP mRNA levels gradually declined, and the maximum reduction in the mRNA level (>50%) was observed at 36 hours, after which the mRNA level started to recover. CETP activity in the culture medium declined over 72 hours. The maximum reduction in CETP activity was observed at 36 hours (53.8% of control). Neither CETP mRNA nor CETP activities changed throughout the experiment after the transfection of sense phosphorothioate ODNs delivered by dpGapoE complex or naked antisense ODNs. We conclude that (1) the novel synthetic dpGapoE was a highly effective and nontoxic vehicle for the nuclear delivery of antisense ODNs into hCETP-CHO cells and (2) antisense ODNs selectively inhibited both CETP expression and activity in an hCETP-CHO cell line. This approach may enable gene regulation in vivo and could possibly be used as an antiatherosclerotic agent to alter high density lipoprotein metabolism.
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Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.