2016, Cilt 46, Sayı 2, Sayfa(lar) 051-057 |
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Antisense Oligonucleotids and Antibacterial Use |
Yamaç TEKİNTAŞ1, Devrim DEMİR-DORA2, Mine HOŞGÖR-LİMONCU1 |
1Ege Üniversitesi Eczacılık Fakültesi, Farmasötik Mikrobiyoloji Anabilim Dalı, İzmir 2Akdeniz Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, Antalya |
Keywords: Antisense oligonucleotides, gene silencing, antisense antibacterials |
The antisense treatment strategy is to use
oligodeoxyribonucleotides for the purpose of silencing
various genes before they start producing proteins. The
antisense mechanism is established by binding
oligonucleotide strands to the target mRNA by way of
Watsons-Crick base pairing. After binding, two basic
pathways prevent the relevant gene from producing protein.
The first of these is the formation of RNase H-mediated
degradation by the oligonucleotide at the site of binding.
Production of protein is hindered because translation
becomes impossible from the gene strand that was broken
down by the RNase enzyme. The second occurs when the
oligonucleotide binds and closes the relevant gene site. In
this way, ribosome is sterically hindered from reading the
gene strand, posttranscriptional procedures are hindered
and the gene cannot make production.
Various chemical modifications of these molecules to
protect them from nucleases was performed. According to
these modifications antisense oligonucletoides (ASO) can
be divided into generations. Despite the protection from
nucleases with modifications they have limited access to
the cell interior. In order to eliminate this restriction it is
necessary to use various methods such as peptide
conjugates, lipid based carrier systems.
ASO sequences can be used as antibacterials by inhibition of
essential genes for bacteria. Besides bacteria can be made
susceptible by oligonucleotides targeting the resistance
genes. The antisense treatment strategy which is not affected
by antibiotic resistance mechanisms, attracts the attention of
many scientist. General properties of these molecules, mode
of action and studies involving the use of these molecules in
bacterial eradication are summarized in this review.
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