The Molecules of HIV

Note: this site last updated in 2006

Antisense oligonucleotides

An article from "The Molecules of HIV" (c) Dan Stowell

"Antisense oligonucleotides" sounds at first like a bizarre piece of jargon.

DNA in a cell normally consists of two DNA strands, twisted into a double helix and attached to each other by intermolecular attractions. The pattern of bases on one strand is "antisense" to the other one, in that the pattern is complementary, allowing the two strands to fit together like a jigsaw. RNA is generally found as a single strand - for example messenger RNA (mRNA), which carries the genetic code from cellular DNA to the cellular ribosomes (which sysnthesise protein).

The mRNA needs to be able to interact properly with the ribosomes. If we could find a stretch of nucleotides which could attach to a specific mRNA (just like one strand of DNA associates with another), then we could stop this mRNA interacting properly with the ribosomes and stop the production of the protein encoded by the mRNA.

Antisense oligonucleotides do just this. They are stretches of between 2 and 20 nucleotides, devised to be complementary to a specific type of mRNA. If we can get antisense oligonucleotides into a cell which bind with mRNA representing HIV protein, for example, then hopefully we can inhibit an infected cell's HIV production.

A perfect solution? Unfortunately not. The body often reacts to antisense oligonucleotides as foreign invaders and attacks them. Also, antisense oligonucleotides are readily degraded by enzymes found throughout the human body, such as DNase. Some side-effects have also been found in animal studies.

A related strategy is RNA-interference">RNA-interference, which uses small pieces of complementary RNA to interfere with gene expression.

Written by
Dan Stowell

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