L. Mologni et al., In vitro transcriptional and translational block of the bcl-2 gene operated by peptide nucleic acid, BIOC BIOP R, 264(2), 1999, pp. 537-543
Citations number
34
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
The antisense and antigene activity of peptide nucleic acid (PNA) targeted
to the human B-cell lymphoma (bcl)-2 gene was evaluated in vitro. Several P
NAs complementary to different sequences of bcl-2, including the start codo
n and the 5'-untranslated region (5'-UTR), were tested. One PNA directed ag
ainst the AUG start codon and another recognizing the 5'-UTR were able to s
pecifically reduce Bcl-2 protein synthesis in a cell-free system; however,
only partial inhibition (80 and 54%, respectively) was obtained when they w
ere used singularly. Complete translation block was obtained with the simul
taneous presence of both PNAs. A tripler-forming bis-PNA was targeted to a
homopurine sequence on the coding strand of the bcl-2 cDNA. In an in vitro
transcription assay this PNA specifically inhibited the transcription of bc
l-2 at concentrations as low as 300 nM, with the concomitant appearance of
a truncated 200-base-long product. These results demonstrate the ability of
PNA to selectively modulate both translation and transcription of bcl-2 in
vitro and suggest its potential use as an antisense and an antigene agent
in order to downregulate bcl-2 expression in tumors, (C) 1999 Academic Pres
s.