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Nucleic Acids Research, 2000, Vol. 28, No. 10 2153-2157
© 2000 Oxford University Press

Targeted elimination of zygotic messages in Xenopus laevis embryos by modified oligonucleotides possessing terminal cationic linkages

John M. Dagle*, Jennifer L. Littig, Lillian B. Sutherland1 and Daniel L. Weeks1

Department of Pediatrics and 1Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA

We have designed a new class of modified antisense oligodeoxyribonucleotides (ODN) consisting of a central contiguous stretch of 6–8 unmodified nucleotides flanked by 3'- and 5'-regions containing several nucleotides joined by cationic internucleoside linkages. The positive charge results from modification of the internucleoside linkages as N,N-diethylethylene­diamine phosphoramidates. These zwitterionic compounds show improved antisense activity in both Xenopus oocytes and embryos compared to our previously described chimeric oligonucleotides possessing neutral terminal internucleoside linkages. Using the localized maternal mRNA An2 as a target, we have shown that chimeric oligonucleotides with terminal positive charges are very effective in the sequence-specific elimination of maternal messages present in both oocytes and embryos. In addition, using the embryonic mRNA GS17 as a target, we have shown that these oligonucleotides can direct RNase H-mediated cleavage of messages produced at the onset of zygotic transcription, after the mid-blastula stage. These new compounds should be useful in attenuating embryonic gene expression to study the role of specific proteins in early vertebrate development.

* To whom correspondence should be addressed at: Department of Pediatrics, W216-GH, 200 Hawkins Drive, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. Tel: +1 319 353 7009; Fax: +1 319 356 4685; Email: john-dagle@uiowa.edu


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