GOLD nanoparticles could be an ideal way of delivering one of the hottest prospects in molecular medicine. The nanoparticles have successfully carried RNA molecules into human cells, where researchers hope they can be used to tackle everything from HIV to cancer.
Over the past few years, stretches of 鈥渟hort interfering鈥� RNA, or siRNA, which are just over 20 bases long, have emerged as a powerful tool in biology because they are able to 鈥渢urn off鈥� target genes. They do this by selectively interfering with the messenger RNA that is the intermediate step between a gene and the protein it codes for.
This means that siRNAs could also act as exquisitely targeted drugs, shutting down key genes from HIV and other viruses, or disabling the human genes linked with conditions from age-related sight loss to cancer.
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鈥渟iRNAs could act as exquisitely targeted drugs, shutting down genes from HIV and other viruses鈥�
Getting large quantities of siRNA into human cells and protecting it from being broken down too quickly once inside is a tough challenge, however. Now a team led by of Northwestern University in Evanston, Illinois, has used gold nanoparticles to carry siRNA into cultures of human cells.
The team鈥檚 delivery system consists of balls of gold just 13 nanometres across, each bearing about 30 short stretches of RNA bound to the gold by a connecting molecule. When these particles were added to human cell cultures, they entered 99 per cent of the cells within 6 hours. 鈥淭hese particles go in better than anything else,鈥� says Mirkin, although the mechanism of absorption is unclear.
The researchers then tested how well the gold-borne siRNAs did their job. They added siRNA-laden particles to cells carrying a loop of DNA bearing the gene for luciferase, the enzyme that gives fireflies their glow. A control group of cells was given the siRNA alone. Four days later, the reduction in the activity level of the gene in the gold-dosed cells was more than double the drop found in the control cells (Journal of the American Chemical Society, ).
鈥淲e can increase the lifetime of siRNA from minutes to hours 鈥� and sometimes even days,鈥� says Mirkin. He reckons that as RNA is a salt, its high density on the particles鈥� surfaces creates an environment that inhibits the enzymes that break down RNA.
, an siRNA specialist at the City of Hope hospital in Duarte, California, is impressed that Mirkin鈥檚 team could deliver large amounts of siRNA to their cultured cells without obvious toxicity. Other delivery systems, such as lipids, tend to be toxic to cells at high doses, he notes.
The next test will be to find out whether the particles perform as well in a living body as in the culture dish. 鈥淚t鈥檚 early days, and there are a lot of delivery vehicles that work in cultured cells and haven鈥檛 worked in animals,鈥� cautions , a gene therapist at Stanford University.
