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Nucleic Acids Research, 2003, Vol. 31, No. 21 6064-6078
© 2003 Oxford University Press

Therapeutic modulation of endogenous gene function by agents with designed DNA-sequence specificities

Taco G. Uil1,2, Hidde J. Haisma2 and Marianne G. Rots*,2

1 Department of Molecular Cell Biology, Leiden University Medical Center, Leiden and 2 Department of Therapeutic Gene Modulation, University Center for Pharmacy, PO Box 196, 9700 AD Groningen, The Netherlands

*To whom correspondence should be addressed. Tel: +31 50 363 7866; Fax: +31 50 363 7953; Email: m.g.rots{at}farm.rug.nl

Designer molecules that can specifically target pre-determined DNA sequences provide a means to modulate endogenous gene function. Different classes of sequence-specific DNA-binding agents have been developed, including triplex-forming molecules, synthetic polyamides and designer zinc finger proteins. These different types of designer molecules with their different principles of engineered sequence specificity are reviewed in this paper. Furthermore, we explore and discuss the potential of these molecules as therapeutic modulators of endogenous gene function, focusing on modulation by stable gene modification and by regulation of gene transcription.


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