Targeted elimination of zygotic messages in Xenopus laevis embryos by modified oligonucleotides possessing terminal cationic linkages
Targeted elimination of zygotic messages in Xenopus laevis embryos by modified oligonucleotides possessing terminal cationic linkages
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DOI：
10.1093/nar/28.10.2153
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发表时间：
2000-05-15
影响因子：
14.9
通讯作者：
Weeks, DL
中科院分区：
文献类型：
--
作者：
Dagle, JM;Littig, JL;Weeks, DL
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 midblastula stage. These new compounds should be useful in attenuating embryonic gene expression to study the role of specific proteins in early vertebrate development.
