Inhibition of influenza virus replication by phosphorothioate and liposomally endocapsulated oligonucleotides

被引:8
作者
Abe, T
Hatta, T
Takai, K
Nakashima, H
Yokota, T
Takaku, H [1 ]
机构
[1] Chiba Inst Technol, Dept Ind Chem, Chiba 275, Japan
[2] Kagoshima Univ, Sch Dent, Dept Microbiol & Immunol, Kagoshima 890, Japan
[3] Rat Drug Design Labs, Fukushima 96012, Japan
关键词
D O I
10.1080/07328319808005191
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have demonstrated that antisense phosphorothioate oligonucleotides (S-ODNs) inhibit influenza virus A replication in MDCK cells. Phosphorothioate and liposomally encapsulated oligonucleotides with two target sites (PB1 and PB2) were synthesized and tested for virus-induced cytopathogenicity effects by a MTT assay using MDCK cells. The liposomally encapsulated S-ODNs complementary to the sites of the PB2-AUG initiation codon showed highly inhibitory effects. On the other hand, the inhibitory effect of the liposomally encapsulated S-ODNs targeted to PB1 was considerably decreased in comparison with the PB2 target sites. The liposomally encapsulated oligonucleotides exhibited higher inhibitory activity than the free oligonucleotides. The activities of the modified oligonucleotides are effectively enhanced by using the liposomal carrier.
引用
收藏
页码:471 / 478
页数:8
相关论文
共 28 条
[1]   LIPOSOME DELIVERY OF ANTISENSE OLIGONUCLEOTIDES - ADSORPTION AND EFFLUX CHARACTERISTICS OF PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES [J].
AKHTAR, S ;
JULIANO, RL .
JOURNAL OF CONTROLLED RELEASE, 1992, 22 (01) :47-56
[2]   TRANSCRIPTION ANTITERMINATION DURING INFLUENZA VIRAL TEMPLATE RNA-SYNTHESIS REQUIRES THE NUCLEOCAPSID PROTEIN AND THE ABSENCE OF A 5' CAPPED END [J].
BEATON, AR ;
KRUG, RM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (17) :6282-6286
[3]  
BRAAM J, 1983, CELL, V34, P609
[4]  
ERICKSON RP, 1992, GENE REGULATION BIOL
[5]   SPECIFIC REGULATION OF GENE-EXPRESSION BY ANTISENSE, SENSE AND ANTIGENE NUCLEIC-ACIDS [J].
HELENE, C ;
TOULME, JJ .
BIOCHIMICA ET BIOPHYSICA ACTA, 1990, 1049 (02) :99-125
[6]   THE AUTOMATED SYNTHESIS OF SULFUR-CONTAINING OLIGODEOXYRIBONUCLEOTIDES USING 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE AS A SULFUR-TRANSFER REAGENT [J].
IYER, RP ;
PHILLIPS, LR ;
EGAN, W ;
REGAN, JB ;
BEAUCAGE, SL .
JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (15) :4693-4699
[7]   COMPLETE NUCLEOTIDE-SEQUENCE OF THE POLYMERASE-3 GENE OF HUMAN INFLUENZA VIRUS-A/WSN/33 [J].
KAPTEIN, JS ;
NAYAK, DP .
JOURNAL OF VIROLOGY, 1982, 42 (01) :55-63
[8]   ANTI-HIV ACTIVITIES AND PHYSICOCHEMICAL PROPERTIES OF PHOSPHOROTHIOATE ANALOGS COMPLEMENTARY TO HIV SEQUENCES [J].
KIM, SG ;
KANBARA, K ;
NAKASHIMA, H ;
YAMAMOTO, N ;
MURAKAMI, K ;
TAKAKU, H .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1993, 3 (06) :1223-1228
[9]   PHOSPHOROTHIOATE ANALOGS OF OLIGODEOXYRIBONUCLEOTIDE - SYNTHESIS AND ACTIVITY AS INHIBITORS OF REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS [J].
KIM, SG ;
SUZUKI, Y ;
NAKASHIMA, H ;
YAMAMOTO, N ;
TAKAKU, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 179 (03) :1614-1619
[10]   INHIBITION OF INFLUENZA-VIRUS REPLICATION BY PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES [J].
LEITER, JME ;
AGRAWAL, S ;
PALESE, P ;
ZAMECNIK, PC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (09) :3430-3434