Exploring Free Energy Conversion Processes Could Aid Gene Delivery Research

Originally Published MDDI March 2003

R&D DIGEST

Research at Purdue University (West Lafayette, IN) in 1998 produced a tiny motor from synthetic biological molecules, suggesting that RNA molecules can perform physical work. More recent efforts by the team could lead to critical advances in medical applications of nanotechnology. The researchers have also found that RNA is able to bind adenosine triphosphate (ATP), which is required to transfer metabolic energy in living things. Among the potential uses are nanoscale gene-delivery mechanisms. 

Current research has been focused specifically on how viral RNA molecules bind the energy-bearing organic molecule known as ATP. The Purdue team found that linking the two substances can enable a fundamental storehouse of information to be moved by what is essentially one of its fuels. The team included Peixuan Guo, DVM, PhD, and Dan Shu, PhD, of the university's department of pathobiology and Purdue Cancer Center. They believe that the discovery could aid understanding of the fundamental role that RNA plays in the creation of living things. 

DNA, RNA, and ATP have been shown to be fundamental components of various life processes. More precise knowledge regarding their various functions, however, is still being explored. "There are thousands of kinds of RNA in your body," Guo said. "Most varieties have an unknown function. When ribozymes were discovered, it taught us that RNA was probably responsible for the creation of other complex biological molecules. RNA might be more significant to life on Earth than we imagined a few years ago."

Guo suggests that "RNA could be even more of a key player than we realize. The fact that it can be made to bind ATP in the phi29 virus could imply that these two molecules were among the first to partner in Earth's dance of life."

"You couldn't live for one second without ATP," says Guo. He also suggests that because RNA can bind ATP, it might be able to direct the release of the energy required to create life. "We are just beginning to learn about RNA's many functions," he said. "But it is possible that it plays a crucial role in metabolism, too. In that case, RNA would play a more central role in biology than we originally thought. We are seeking fundamental knowledge here."

Among the first practical applications of their discovery has been the construction of a tiny motor capable of limited types of work. "I think RNA can be made to do mechanical work," Guo says. "ATP binding could power a motor made of six strands of RNA, and we are now exploring the myriad possible applications of such a tiny mechanism." 

He explains that the team has learned to assemble several strands of RNA into a hexagonally shaped "engine" with a strand of DNA functioning as the axle. Supplied with ATP fuel, the RNA strands function like pistons to turn the axle. They speculate that such tiny motors could find applications in nanotechnology. Says Guo, "The world's smallest machines will need equally small motors to propel them. Ours uses organic molecules as fuel, so no special power source would need to be developed." 

The motors could not only be used to spin the DNA strand, but also as potential gene-delivery vehicles. The team previously determined that such a motor could drive its axle into a virus's protein shell. 

More recently, they found that the ATP-binding RNA derived from the phi29 virus can deliver a ribozyme that destroys hepatitis B. Guo says one goal of gene therapy is to deliver healthy genes or therapeutic molecules into damaged cells. He adds that, "With some modifications, we hope our research will enable us to deliver therapeutic molecules to cancerous or other virus-infected cells as well." 

The researchers believe that more work is needed on RNA's fundamental capabilities. "We would like to find other examples of how RNA operates in the body," says Guo. "We know from our research that RNA can be made to perform physical work in a viral system and in the laboratory, so it is possible that it is also involved in the transportation of components within cells."

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