PMID- 8917339
OWN - NLM
STAT- MEDLINE
DCOM- 19961218
LR  - 20101118
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 16
IP  - 5A
DP  - 1996 Sep-Oct
TI  - Effects of liposomal antisense oligonucleotides on mRNA and protein levels of the 
      HPV 16 E7 oncogene.
PG  - 2485-92
AB  - Despite the known association of human papillomavirus (HPV) infection with 
      cervical cancer there is no specific antiviral treatment for HPV infection. 
      Antisense oligode-oxynucleotides (AS-ODNs) may offer an effective way to treat 
      HPV infections as the stability and delivery have been improved using modified 
      ODNs or carrier systems. In this study we investigated the effects of liposomal 
      AS-ODNs (0.1, 1 and 5 microM) on HPV 16 E7 mRNA and protein levels in CaSki 
      cells. We used cationic liposomes (10 microM) containing 
      dimethyldioctadecylammonium bromide (DDAB) or 
      2,3-dioleyloxy-N-[2(sperminecar-boxamido)ethyl]-N, N-dimethyl-1-propanaminium 
      trifluoroacetate (DOSPA). Both these liposomes had 
      dioleoylphosphatidyl-ethanolamine (DOPE) as a helper lipid. The target of the 
      AS-ODNs was E7 protein because it is the one of the two oncoproteins of HPV 16. 
      Only liposomal AS-ODNs which were targeted to the initiation codon of E7, had an 
      effect on E7 mRNA expression; two shorter transcripts were detected, suggesting 
      that RNase H degradation was activated. Liposomal random ODN or liposomal ODN 
      targeted downstream from the initiation site of E7 did not affect the mRNA 
      pattern. However, no change was found in the E7 protein levels detected by 
      immunoprecipitation. Further studies showed that AS-ODNs inhibited the 
      translation of E7 mRNA in a rabbit reticulocyte lysate assay. This data, together 
      with the changes in mRNA levels, proved that the AS-ODNs reached the target mRNA. 
      One possible explanation for the unchanged protein level of E7 in CaSki cells 
      might be that immunoprecipitation is not sensitive enough to detect minor changes 
      in protein levels. However, further progress is still needed in the field of 
      carrier systems and modifications of AS-ODNs before non-sequence specific effects 
      can be avoided.
FAU - Lappalainen, K
AU  - Lappalainen K
AD  - MediCity Research Laboratory, Faculty of Medicine, University of Turku, Finland.
FAU - Pirila, L
AU  - Pirila L
FAU - Jaaskelainen, I
AU  - Jaaskelainen I
FAU - Syrjanen, K
AU  - Syrjanen K
FAU - Syrjanen, S
AU  - Syrjanen S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Antiviral Agents)
RN  - 0 (Drug Carriers)
RN  - 0 (Liposomes)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Viral)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
SB  - IM
MH  - Antiviral Agents/*pharmacology
MH  - Cell Division/drug effects
MH  - Drug Carriers
MH  - Drug Screening Assays, Antitumor
MH  - Female
MH  - Humans
MH  - Liposomes
MH  - Oligonucleotides, Antisense/*pharmacology
MH  - Oncogene Proteins, Viral/*drug effects/metabolism
MH  - Papillomavirus E7 Proteins
MH  - Protein Biosynthesis/drug effects
MH  - RNA, Messenger/*drug effects/metabolism
MH  - RNA, Viral/*drug effects/metabolism
MH  - Tumor Cells, Cultured
MH  - Uterine Cervical Neoplasms
EDAT- 1996/09/01 00:00
MHDA- 1996/09/01 00:01
CRDT- 1996/09/01 00:00
PHST- 1996/09/01 00:00 [pubmed]
PHST- 1996/09/01 00:01 [medline]
PHST- 1996/09/01 00:00 [entrez]
PST - ppublish
SO  - Anticancer Res. 1996 Sep-Oct;16(5A):2485-92.