Technique serves as a miracle cure-all treatment
genes by activating or inactivating them at the DNA level could
lead to drugs for the treatment or cure of almost any disease, say
researchers
Virtually every disease starts at the level of malfunctioning gene expression, or viral or bacterial gene expression. Current techniques for turning genes on or off focus on controlling the messenger RNA once it's already produced. But blocking all the copies of messenger RNA before they can make a protein within a cell is impossible.
However, the studies represent significant findings and are the most definitive to date showing that chromosomal DNA and its production is accessible to and can be controlled by synthetic and natural molecules.
Researchers describe how they shut down gene expression in cultured cells by blocking the ability of chromosomal DNA to be copied into RNA and made into proteins.
"With this information, one could easily turn on or off gene expression, as well as think about ways to correct genetic disease by changing mutant gene sequences back to normal," said David Corey, professor of pharmacology and biochemistry.
"Those types of things now look a lot more feasible," he added.
The researchers targeted chromosomal DNA in two ways. First, they developed a synthetic molecule called a peptide nucleic acid, or PNA, which physically binds to DNA and blocks enzymes from copying, or transcribing, the DNA into messenger RNA.
More importantly, the researchers also employed RNA itself as a silencing agent. Previous work by other scientists had shown that RNA might be able to target chromosomal DNA, so once Dr. Corey and his team saw that PNAs were working, they decided to try RNA as well.
Genes are segments of DNA housed in the chromosomes in the nucleus of every cell. Genes carry instructions for making proteins, which in turn carry out all of life's functions. Faulty or mutated genes lead to malfunctioning proteins, which cause disease.
The information in a gene is not directly converted into proteins, but first is copied by special enzymes into many copies of messenger RNA, which then move out of the nucleus and into the body of the cell, where they go on to create a protein.
"The RNA is more important because it may reflect the body's own natural mechanism for controlling gene expression, while the PNAs are synthetic," Corey said.
The researchers designed their RNA to match up with and target specific genes. "It's possible that the body is making the RNAs that we are using, and that will be an exciting topic for further research, to determine whether the human body or viruses and bacteria make RNA sequences like this to control gene expression," Corey said.
So far, the researchers have inhibited the expression of nine different genes in cancer cell cultures. Dr. Corey said it's not clear whether the RNA is actually binding to the DNA itself, as the PNAs do, but it's clear the effects are occurring at the DNA level.
The two papers appear in the current online edition of the journal Nature Chemical Biology.
