Modulation of Alternative Splicing by Antisense Oligonucleotides

  • P. Sazani
  • R. Kole
Part of the Progress in Molecular and Subcellular Biology book series (PMSB, volume 31)

Abstract

Sequence-specific base pairing is the principle mechanism by which antisense oligonucleotides function as therapeutics and sequence-specific research tools. The same basic mechanism of action is used for regulation of expression of certain genes by living cells. Antisense genes were found in E. coli (Simons and Kleckner 1988) and more recently in C. elegans (Ambros 2000) and in human cells (Hastings et al. 2000). Inhibition of Rous sarcoma virus replication by a synthetic 13-mer antisense DNA molecule (Zamecnik and Stephenson, 1978) provides one of the first examples of the effects of antisense oligonucleotides. For antisense genes and oligonucleotides the assumed or determined function was to decrease the expression of their sense target RNAs. Numerous subsequent papers, involving downregulation of gene expression, reported that DNA oligonucleotides were downregulating gene expression by base pairing to mRNA and eliciting destruction of the RNA in the RNA-DNA duplex by ribonuclease H (RNase H). Modified oligonucleotides that do not elicit RNase H activity or triplex-forming oligonucleotides that interact with DNA targets were also extensively used for downregulation of gene expression. The anti-sense field was extensively reviewed in a recent volume (Crooke 2001).

Keywords

Hepatitis Codon Dementia Lysine Stein 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • P. Sazani
  • R. Kole
    • 1
  1. 1.Lineberger Comprehensive Cancer Center and Department of PharmacologyUniversity of North CarolinaChapel HillUSA

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