Mimic Molecule May Improve Chemotherapy - Brief Article

USA Today (Society for the Advancement of Education), June, 1999

Maybe you can't fool Mother Nature, but that hasn't stopped James K. Bashkin, an assistant professor of chemistry at Washington University in St. Louis (Mo.), from imitating her. He has created a molecule that mimics the behavior of a kind of naturally occurring RNA called a ribozyme, which acts as a catalyst. The molecule can dismantle the dangerous genetic codes involved in propagating viral and fungal diseases, certain cancers, and even the HIV virus.

DNA is a double-stranded molecule, located in the nucleus of every human cell, that carries the genetic plans of the genes contained on 46 chromosomes. RNA is a single-stranded molecule that acts in tandem with DNA and is responsible for carrying out the plans of DNA by directing the formation of proteins.

Bashkin has chemically engineered a new class of DNA molecule that recognizes specific chemical sequences of messenger RNA (mRNA) and destroys them to prevent the making of harmful proteins. The molecule, which he calls a "functional ribozyme mimic," uses water molecules, abundant in cells, in a chemical reaction to attack specific, targeted sequences of mRNA. Because his functional mimic is a catalyst, it is not destroyed in this action, but, instead, remains intact to destroy many more targeted mRNA molecules.

Bashkin's find could lead to cheaper chemotherapy drugs that produce far fewer side effects because his ribozyme mimics recognize the chemistry of dangerous mRNA, leaving the normal mRNA alone. Chemotherapy typically causes severe side effects because the method cannot completely differentiate between healthy and diseased cells.

The ribozyme mimic is designed to be a catalyst that cannot destroy itself, but can destroy many copies of the targeted RNA. Naturally occurring ribozymes may be used in chemotherapy, but they are large, expensive, and fragile RNA molecules. Bashkin's mimics, based on stouter DNA molecules, are smaller, simpler, and lighter than naturally occurring ribozymes and can be made to resist enzyme degradation better.