Antisense Oligodeoxynucleotides

• the monomers are deoxynucleotides like those in DNA
• there are usually only 15-20 of them, hence "oligo"
• their sequence (3´ -> 5´) is antisense; that is, complementary to the sense sequence of a molecule of mRNA.

Antisense ODNs are synthesized in the hope that they can be used as therapeutic agents blocking disease processes by blocking the synthesis of a particular protein. This would be achieved by the binding of the ODN to the mRNA from which that protein is normally synthesized. Binding of the two may

• physically block the ability of ribosomes to move along the messenger RNA or
• simply hasten the rate at which the mRNA is degraded within the cytosol

In order to be useful in human therapy, ODNs must

• be able to enter the target cells
• avoid digestion by DNAse
• not cause unpleasant side-effects

• chemically modified to resist digestion by DNAse
• attached to a targeting device such as
  • the ligand for the type of receptors found on desired target cells
  • antibodies directed against molecules on the surface of the desired target cells

Several laboratories are presently testing antisense ODNs as weapons against:

• HIV-1, the most frequent cause of AIDS in the United States
• cytomegalovirus (CMV); which frequently causes serious complications in AIDS patients
• asthma; inhalation of antisense ODNs reduces (at least in rabbits) the synthesis of cell receptors involved in asthma.
• certain cancers, e.g., chronic myelogenous leukemia (CML)
• certain types of inflammation caused by cell-mediated immune reactions