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Content archived on 2022-12-23

Antisense oligonucleotides: new superspecific compounds controlling growth of mollicutes (mycoplasma)

Objective



It is now firmly established that mollicutes are true eubacteria. They have evolved regressively from gram-positive bacterial ancestors with a low content of guanine plus cytosine in DNA - more specifically from certain clostridia. They are characterised by a small genome size, a small number of rRNA operons and a lack of cell wall. Numerous experiments demonstrated that antisense oligonucleotides and their derivatives are specific inhibitors of gene expression such as influenza virus, HIV and tickborn encephalitis viruses. They are a new generation of potential drugs, capable in a highly specific manner of inhibiting various pathogens.

Taking into consideration this achievement of antisense technology and the unique biological properties of the mollicutes, especially their nucleic acids and the impossibility of synthesising their precursors, it is supposed that the use of original characteristics of DNA and RNA of these mollicutes may activate pathogens of that type.

In this project antisense oliginucleotides which are complementary to different selective regions of signature sequences of 16S rRNA and ribosomal operons on the DNA of mollicutes will be synthesized, and will highly selectively penetrate mycoplasmic cells and suppress the growth of mollicutes. Such oligonucleotides will be considered as potential superspecific antimycoplasmic drugs. Antisense nucleic acids will be tested in vitro using DNA replication and transcription as well as translation (mycoplasmal ribosome assays) systems for the inhibitory effectiveness of antisense oligonucleotides. The most inhibitory antisense nucleic acids will be selected. Moreover different methods of protection of antisense oligonucleotides against nuclease degradation by mollicute enzymes will be studied. Antisense oligonucleotides wil be tested in vivo for an inhibition of mollicutes in their living habitat. Antisense oligonucleotides added to molecules which promote an increased penetration into mollicute cells and hence provide the antisense nucleic acids with a high inhibitory activity will be synthesized.

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Coordinator

Johannes Gutenberg Universität Mainz
EU contribution
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Address
Duesbergweg 6
55099 Mainz
Germany

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Total cost

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Participants (3)

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