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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

A synthetic, chemically modified ribozyme eliminates amelogenin, the major translation product in developing mouse enamel in vivo.

Ribozymes are small RNA structures capable of cleaving RNA target molecules in a catalytic fashion. Designed ribozymes can be targeted to specific mRNAs, blocking their expression without affecting normal functions of other genes. Because of their specific and catalytic mode of action ribozymes are ideal agents for therapeutic interventions against malfunctioning or foreign gene products. Here we report successful experiments to 'knock out' a major translation product in vivo using synthesized, chemically modified ribozymes. The ribozymes, designed to cleave amelogenin mRNA, were injected close to developing mandibular molar teeth in newborn mice, resulting in a prolonged and specific arrest of amelogenin synthesis not caused by general toxicity. No carriers were required to assist cellular uptake. Amelogenins are highly conserved tissue-specific proteins that play a central role in mammalian enamel biomineralization. Ultrastructural analyses of in vivo ribozyme-treated teeth demonstrated their failure to develop normally mineralized enamel. These results demonstrate that synthesized ribozymes can be highly effective in achieving both timed and localized 'knock-out' of important gene products in vivo, and suggest new possibilities for suppression of gene expression for research and therapeutic purposes.[1]

References

  1. A synthetic, chemically modified ribozyme eliminates amelogenin, the major translation product in developing mouse enamel in vivo. Lyngstadaas, S.P., Risnes, S., Sproat, B.S., Thrane, P.S., Prydz, H.P. EMBO J. (1995) [Pubmed]
 
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