Biological Activity of Oligonucleotide-Poly(L-lysine) Conjugates: Mechanism of Cell Uptake

被引:168
作者
Leonetti, Jean-Paul [1 ]
Degols, Genevieve [1 ]
Lebleu, Bernard [1 ]
机构
[1] Univ Montpellier 2, CNRS, UA 1191, Lab Biochim Prot, F-34060 Montpellier, France
关键词
D O I
10.1021/bc00002a010
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
We have previously shown that antisense oligomers linked to poly(L-lysine) (PLL) exhibit antiviral properties against vesicular stomatitis virus (VSV) at concentrations lower than 1 mu M. The conjugation to PLL provides an interesting alternative to natural or neutral oligomers to increase the biological effects of antisense oligomers. The internalization pathway of oligomer-PLL conjugates as compared to unconjugated oligomers has been studied in L929 cells. In parallel to their enhanced antiviral activity, PLL increases greatly the uptake of fluorescently tagged oligomers. This internalization follows a classical endocytic pathway and the oligomer has to be cleaved from PLL in the cell to exhibit an antiviral effect.
引用
收藏
页码:149 / 153
页数:5
相关论文
共 21 条
[1]   INHIBITION OF VESICULAR STOMATITIS-VIRUS PROTEIN-SYNTHESIS AND INFECTION BY SEQUENCE-SPECIFIC OLIGODEOXYRIBONUCLEOSIDE METHYLPHOSPHONATES [J].
AGRIS, CH ;
BLAKE, KR ;
MILLER, PS ;
REDDY, MP ;
TSO, POP .
BIOCHEMISTRY, 1986, 25 (20) :6268-6275
[2]   SEQUENCE OF THE MURINE AND HUMAN CELLULAR MYC ONCOGENES AND 2 MODES OF MYC TRANSCRIPTION RESULTING FROM CHROMOSOME-TRANSLOCATION IN B-LYMPHOID TUMORS [J].
BERNARD, O ;
CORY, S ;
GERONDAKIS, S ;
WEBB, E ;
ADAMS, JM .
EMBO JOURNAL, 1983, 2 (12) :2375-2383
[3]   SYNTHESIS OF ALKYLATING OLIGONUCLEOTIDE DERIVATIVES CONTAINING CHOLESTEROL OR PHENAZINIUM RESIDUES AT THEIR 3'-TERMINUS AND THEIR INTERACTION WITH DNA WITHIN MAMMALIAN-CELLS [J].
BOUTORIN, AS ;
GUSKOVA, LV ;
IVANOVA, EM ;
KOBETZ, ND ;
ZARYTOVA, VF ;
RYTE, AS ;
YURCHENKO, LV ;
VLASSOV, VV .
FEBS LETTERS, 1989, 254 (1-2) :129-132
[4]  
BRASHFORD CL, 1986, J BIOL CHEM, V261, P9300
[5]   NUCLEOTIDE-SEQUENCES OF THE MESSENGER-RNAS ENCODING THE VESICULAR STOMATITIS VIRUS-N AND VIRUS-NS PROTEINS [J].
GALLIONE, CJ ;
GREENE, JR ;
IVERSON, LE ;
ROSE, JK .
JOURNAL OF VIROLOGY, 1981, 39 (02) :529-535
[6]   SPECIFIC ANTIVIRAL ACTIVITY OF A POLY(L-LYSINE)-CONJUGATED OLIGODEOXYRIBONUCLEOTIDE SEQUENCE COMPLEMENTARY TO VESICULAR STOMATITIS-VIRUS N-PROTEIN MESSENGER-RNA INITIATION SITE [J].
LEMAITRE, M ;
BAYARD, B ;
LEBLEU, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (03) :648-652
[7]  
LEONETTI JP, 1989, GENE, V72, P323
[8]   CHOLESTERYL-CONJUGATED OLIGONUCLEOTIDES - SYNTHESIS, PROPERTIES, AND ACTIVITY AS INHIBITORS OF REPLICATION OF HUMAN IMMUNODEFICIENCY VIRUS IN CELL-CULTURE [J].
LETSINGER, RL ;
ZHANG, GG ;
SUN, DK ;
IKEUCHI, T ;
SARIN, PS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (17) :6553-6556
[9]   MODIFIED POLYRIBOINOSINIC-POLYRIBOCYTIDYLIC ACID COMPLEX THAT INDUCES INTERFERON IN PRIMATES [J].
LEVY, HB ;
BAER, G ;
BARON, S ;
BUCKLER, CE ;
GIBBS, CJ ;
IADAROLA, MJ ;
LONDON, WT ;
RICE, J .
JOURNAL OF INFECTIOUS DISEASES, 1975, 132 (04) :434-439
[10]  
LOKE SL, 1989, P NATL ACAD SCI USA, V86, P38474