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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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