The lipid, lipid-like or polymeric materials that are currentlyused are effective, but tend to result in larger particles, Anderson notes, andmight be associated with toxicity. In addition, such particles areheterogeneous, he adds, "a collection of particles within a certain size rangeand composition." The origami particles the team has constructed, however, aremonodisperse and molecularly identical, which Anderson says allows them to"control the shape and ligand presentation within the particle in a way wecan't do with self-assembling particles."
In mouse studies, the nucleic acid nanoparticles were shownto circulate in the bloodstream with a half-life of 24 minutes, which gave themenough time to reach their targets. According to Anderson, the DNA tetrahedronappeared to protect the RNA from being rapidly absorbed and excreted by thekidneys. The nanoparticles also effectively accumulated at the tumor sites. TheRNA attached to the tetrahedrons was designed to target a gene for luciferase,which had been added to the tumors to make them glow, and in treated mice,luciferase activity was more than cut in half.
The next step for the research is to spread out intotargeting other genes and other genetic diseases.
"We are looking at the utility of these particles in othertumors, in particular ovarian, and with other ligands, and also optimizingtheir size and shape," says Anderson.
Theresearch was funded by the
National Institutes of Health, the
Center for CancerNanotechnology Excellence, Alnylam Pharmaceuticals and the
National ResearchFoundation of Korea, and appeared in the June 3 issue of
Nature Nanotechnology. The paper's lead author is Hyukjin Lee, aformer MIT postdoctoral and current assistant professor at
Ewha WomansUniversity in Seoul, South Korea.
