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Minerva Biotecnologica 2003 September;15(3):167-71

Copyright © 2004 EDIZIONI MINERVA MEDICA

language: English

Targeted gene correction mediated by chimeric RNA/DNA oligonucleotides

Cervelli T., Galli A., Rainaldi G.

Laboratory of Molecular and Gene Therapy, Institute of Clinical Physiology, CNR, Pisa, Italy


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Targeted gene correction by chimeric RNA/DNA oligonucleotides (RDOs) have been developed as strategy for site-specific correction of point mutations located either at episomal or chromosomal targets. This approach could represent the ideal one for application in the gene therapy of single gene diseases because it would correct a mutation directly, without any change in the nuclear genome. The targeted gene correction relies on the formation of specific hybridization of the RDO to the target gene generating a mismatch with the target gene mutation. Then, endogenous repair systems recognize the mismatch and restore the gene function. In this review, we present the recent results obtained in several systems and discuss the possible mechanisms and gene functions involved. Experimental data indicate that Rad51, Msh2 but not Rad52 are likely to be involved in targeted gene correction by RDOs. However, to better understand the potentiality of this strategy for gene therapy applications, other investigations to define the exact contribution of specific DNA repair funtions are necessary.

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