Treating Cancer with RNA Nanotechnology - RNA

Treating Cancer with RNA Nanotechnology
9/15/05
Elizabeth Tolchin
Advantage Business Media
Using RNA nanotechnology researchers say they constructed delivery vehicles that can carry anticancer therapeutic agents directly to infected cells. The team demonstrated the use of the nanodevices against cancer growth in mice and human cells.
"RNA has immense promise as a therapeutic agent against cancer but, until now, we have not had an efficient system to bring multiple therapeutic agents directly into specific cancer cells where they can perform different tasks," says Peixuan Guo, PhD, professor, molecular virology, Purdue University, West Lafayette, Ind., who led the research team from Purdue, the University of Central Florida, and the University of California, Riverside. Applying nanotechnology may offer a solution to RNA delivery, he says.
The research appears in two related papers recently published in the scientific journals Nano Letters [A. Khaled, et al., vol. 5, pp. 1797-1808, (2005)] and Human Gene Therapy (S. Guo, et al., vol. 16, no. 9, pp. 1097-1109S, (2005)].
In their work creating nanostructures from RNA, Guo's team began to see that they could build different kinds of therapeutic RNA onto the RNA scaffolds they created to produce a nanodevice that could transport therapeutic molecules for the prevention or treatment of diseases.
The nanostructures Guo and his team created are made from pRNA, a form of RNA that mimics those in a bacteria-killing virus called phi29. These pRNA strands can be linked to other types of RNA to form longer, hybrid strands with properties the researchers could assign.
"We looked around for RNA strands that would behave in certain ways when they encounter a cancer cell because each of them needs to perform one step of the therapy," Guo says. "An effective agent against cancer needs to accomplish several tasks. It needs first to recognize the cancer cell and gain access to its interior, and then it needs to destroy it. But we'd also like the agent to leave a trail for us, to mark the path the molecule has taken somehow. That way, we can pinpoint the location of the cancer and trace the outcome after the treatment."
To accomplish these tasks, the team turned to small interfering RNA (siRNA), RNA aptamers that bind to cancer cell surface markers, and ribozymes, which can be designed to degrade specific RNA in cancer cells or viruses.
The researchers linked each of the three therapeutic strands with a piece of pRNA, forming three hybrid strands. Then, using techniques learned from their earlier work, they were able to combine all three into triangles or trimers that are between 25 and 40 nanometers wide. ?This is the ?Goldilocks? size for any nanoparticle that is to be used in the body?not too big, not too small,? says Guo.
Incubation of cancer cells with the pRNA trimer that included the receptor-binding RNA aptamer, the gene-silencing siRNA, and ribozyme, resulted in their binding and entry into the cells, and the interrupted growth of human breast cancer cells and leukemia model lymphocytes.
When tested in living mice that were in the process of developing cancer the team found that the nanoparticles completely blocked cancer development. A second group of mice tested with mutated inactive RNA all developed tumors.
The results are very promising, Guo says, but more work needs to be done to ensure that the nanoparticles safely target cancerous cells and are stable enough to avoid degradation by enzymes in the body.