Drugs target RNA to kill tumors ... and block HIV.

Most antitumor drugs destroy their targets by attacking cancer cells' DNA, aiming to kill off the malignancy by disrupting the fast-growing cells' reproductive machinery.

That's a perfectly reasonable strategy, says Sidney M. Hecht, a chemist at the University of Virginia in Charlottesville. But it has one serious drawback: It's not very selective.

Antitumor drugs tend to kill off all growing cells in one fell swoop. While doing the most damage to those proliferating most quickly--tumor cells--they also harm many healthy cells.

An alternative approach, Hecht says, involves targeting RNA. A molecule critical to cellular replication, RNA should prove easier to target selectively. But until recently, scientists have lacked the structural information on RNA that they need to cook up such compounds.

Now, Hecht and University of Virginia chemist Angela Snow report that bleomycin, an antitumor agent known to break up DNA, also chops up RNA in at least one type of bacteria.

"This is good news," Hecht says, because the finding indicates the existence of a previously unidentified mechanism for damaging RNA--a mechanism that chemists can perhaps exploit through carefully designed molecules.

A naturally occurring compound produced by bacteria, bleomycin effectively kills several soft-tissue cancers, such as tumors of the skin, lung, and ovaries. Physicians also use the drug to treat Hodgkin's disease, a lymph cancer.

The new finding that bleomycin can split up RNA inside live bacteria means that carefully crafted anticancer agents may someday strike vulnerable spots in tumor cell growth without damaging healthy tissue.

While Hecht admits that such a project will take many years, in the short run he and his colleagues plan to look at bleomycin's effect on RNA in animal and human cells.

. . . and block HIV 

The RNA-damage strategy may also curb HIV infections, says Anthony W. Czarnick, a chemist at Parke-Davis in Ann Arbor, Mich. After screening 130,000 molecules, he and his colleagues have found a class of 149 compounds that block RNA activity in HIV-1, the AIDS-causing virus.

His team is looking to cripple the virus with small, easily manufactured molecules that block the ability of the virus' RNA to reproduce. Specifically, Czarnick's group is investigating agents that stick to and disable a chunk of the RNA, known as trans- activation response (TAR) RNA. They chose that particular piece of RNA because a critical protein known as TAT binds there.

"We have evidence that preventing the protein TAT from binding to TAR RNA dramatically decreases the replication of cells infected with HIV," Czarnick says. "So the target of our research is the TAT-TAR binding site. We believe that a drug which keeps these two components from interacting will suppress an HIV infection if the drug can reach its target."

Czarnick says that his group's bioassays have shown that the identified agents "clearly inhibit this interaction." The question now, he says, is which ones to target for more study.