[CITATION][C] Uses of antisense nucleic acids—an introduction

ADB Malcolm - Biochemical Society Transactions, 1992 - portlandpress.com
ADB Malcolm
Biochemical Society Transactions, 1992portlandpress.com
The realization that translation of mRNA molecules could be inhibited by suitable
complementary nucleic acids dates back to 1977 [l]. Although Miller et al. originally used an
antisense oligodeoxynucleotide (ODN), further applications were held up by the difficulty
and expense of obtaining the necessary range of ODNs. This was dramatically changed by
the development of inexpensive automated ODN synthesizers using a reliable chemistry
based on the use of phosphoramidites [Z]. Later, the development of transgenic organisms …
The realization that translation of mRNA molecules could be inhibited by suitable complementary nucleic acids dates back to 1977 [l]. Although Miller et al. originally used an antisense oligodeoxynucleotide (ODN), further applications were held up by the difficulty and expense of obtaining the necessary range of ODNs. This was dramatically changed by the development of inexpensive automated ODN synthesizers using a reliable chemistry based on the use of phosphoramidites [Z]. Later, the development of transgenic organisms [3-51 enabled antisense RNA to be produced in vivo, thus eliminating one of the major problems-that of the introduction of large negatively charged molecules into cells. The subsequent papers will address a variety of topics where antisense ODNs and RNAs are finding applications in agriculture, cell biology, developmental genetics and clinical medicine as well as fundamental studies in biochemistry. The technology depends on the fact that while most DNA is double stranded, RNA is predominantly single stranded and is usually only transcribed from one strand (although see Wolfgang Nellen’s paper later in this colloquium). Hence a DNA sequence complementary to the strand which is not transcribed is therefore complementary to this RNA. Such an antisense sequence can therefore bind to this RNA and thereby inhibit translation. With the correct choice of sequence, such inhibition can have a profound effect on the cell, the tissue and the organism.
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