Short peptide nucleic acids (PNA) inhibit hepatitis C virus internal ribosome entry site (IRES) dependent translation in vitro.

Abstract:

:The internal ribosome entry site (IRES) of hepatitis C virus (HCV) which governs the initiation of protein synthesis from viral RNA represents an ideal target for antisense approaches. Using an original bicistronic plasmid, we first established that sequence and translational activity of HCV IRESs cloned from six patients, whether responders or not to combination therapy, were conserved. We then tested the hypothesis that antisense molecules, i.e. short peptide nucleic acids (PNA), could inhibit HCV translation by binding to the highly conserved IIId or IV loop regions of the IRES. Five 6-10mer PNAs were designed. They strongly inhibit HCV IRES-driven translation in a rabbit reticulocyte lysate assay. This inhibition was highly specific since corresponding PNAs with only one mismatch were inactive. Short phosphorothioate oligonucleotides of same sequence were unable to inhibit HCV translation. PNA molecule was shown to have anti-HCV activity in Huh-7.5 cells when electroporated with a full-length HCV genome construct. Using oligonucleotide as carrier, PNA was also transfected in HCV replicon-harboring cells and in JFH1 infected Huh-7.5 cells.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Alotte C,Martin A,Caldarelli SA,Di Giorgio A,Condom R,Zoulim F,Durantel D,Hantz O

doi

10.1016/j.antiviral.2008.06.011

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

280-7

issue

3

eissn

0166-3542

issn

1872-9096

pii

S0166-3542(08)00330-6

journal_volume

80

pub_type

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