The promise of short interfering RNA (siRNA) is that it can be harnessed to turn off harmful genes in the cell. The difficulty is getting siRNA into the cell in the first place. In a new approach, nanoengineers have driven siRNA into the cell on acoustically-propelled nanomotors, silencing genes faster and more completely than with current methods (ACS Nano2016, DOI: 10.1021/acsnano.6b01415).
To silence a gene, researchers tap the cell’s own gene suppression system, which quashes the RNA messengers that are produced when a DNA sequence is expressed. The messengers are knocked out by siRNA, complementary to a given messenger RNA, which binds the mRNA and prevents it from being translated into a protein. Scientists can mooch off the cell’s gene suppression infrastructure simply by inserting an engineered siRNA specific to a target into the cell.
But that’s easier said than done. The negatively charged siRNA has to cross a negatively-charged cell membrane, traverse the intracellular milieu, and bump into the cell’s silencing complex before degradation enzymes destroy it.
The delivery challenge has spawned a bounty of possible siRNA carriers: metal particles, lipid bubbles, hydrogels, and more. Most of these strategies rely on some form of chemical camouflage to enter the cell and on diffusion to do the rest. But Yi Chen and Joseph Wang of the University of California, San Diego, thought that ultrasound-propelled nanowires might produce an siRNA transporter with more oomph.
When bombarded with ultrasound, these tiny gold rods—about 4 μm long, 200 nm in diameter, and concave at one end—scurry into motion. They penetrate cells, bounce around like pinballs, and even spin.
Via Integrated DNA Technologies