Treating Cancer With RNA Nanotechnology

Using strands of genetic material, Purdue University scientists have constructed tiny delivery vehicles that can carry anticancer therapeutic agents directly to infected cells, offering a potential wealth of new treatments for chronic diseases. The vehicles look nothing like delivery trucks, though that is their function once inside the body. Instead, these so-called nanoparticles, which are assembled from three short pieces of ribonucleic acid, resemble miniature triangles. The microscopic particles possess both the right size to gain entry into cells and also the right structure to carry other therapeutic strands of RNA inside with them, where they are able to halt viral growth or cancer's progress. The team has already tested the nanoparticles successfully against cancer growth in mice and lab-grown human cells.

This triangular particle, which is about 25 billionths of a meter across, could become one of nanotechnology's contributions to the fight against cancer. Three strands of RNA are linked together to form this "nanoparticle." Each of the strands is spliced together from two kinds of RNA - one sort serves as a scaffold and dovetail to hold the particle together; while the other carries a hunter to find cancer cells, a marker to detect the target, or genetic instructions deadly to a cancer cell. (Guo Laboratories)

The research team created their nanoparticles by linking together different kinds of RNA, a task that their previous research has given them ample opportunities to practice. Several years after building a tiny "motor" from several strands of RNA that mimic those in a bacteria-killing virus called phi29, the team learned how to manipulate these stringy molecules into different shapes, including rods, triangles and arrays.

RNA molecules come in many variant forms, and the sort that the team mimicked from the phi29 virus – called pRNA – also can be linked to other types of RNA to form longer, hybrid strands with properties the researchers could assign.

According to the researchers, 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. Additionally, it would be beneficial if the agent somehow left a trail to mark the path the molecule had taken. That way, the location of the cancer could be pinpointed and the outcome could be traced after the treatment.

To accomplish these tasks, the team turned to other forms of RNA that can interfere with the goings-on inside cells. The team sorted through a variety of RNA forms that have shown promise for disease treatment and found three that could perform each of the desired tasks. One example is "small interfering RNA," or siRNA, which deactivates certain genes in cells. The others are RNA aptamers, which bind to cancer cell surface markers, and ribozymes, which can be designed to degrade specific RNA in cancer cells or viruses.

Particles larger than about 100 nanometers are generally too large to pass through cell membranes into the cell's interior and the body has a hard time retaining particles smaller than 10 nanometers. But the tiny triangles fit, and they worked well enough to interrupt the growth of human breast cancer cells and leukemia model lymphocytes in laboratory experiments.

Additionally, the team found that the nanoparticles completely block cancer development in living mice. A group of mice that were in the process of developing cancer were tested with the nanoparticles, and they did not develop the disease. A second group that was tested with mutated inactive RNA all developed tumors.

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