Dynamic Delivery

Microscopic sponges made entirely of RNA enable efficient gene silencing.

By | July 1, 2012

RNA interference is a powerful gene silencing technique in the culture dish, but harnessing that power for potential clinical use is not straightforward. Delivering short interfering RNAs (siRNAs) to target cells in the body is difficult, explains MIT’s Paula Hammond, “because siRNA gets easily degraded, so you need to start out with a lot to allow for significant loss.”

Researchers have traditionally complexed or encapsulated siRNA molecules with various types of polymers or lipids with the aim of protecting the siRNA in transit and assisting its uptake into cells. But such polymers can be toxic, especially when used in the large amounts necessary to protect siRNAs.

“[We wanted] to make a system where the cargo was its own carrier,” says Hammond, whose research team came up with a potential solution to the polymer problem. Her team synthesized strings of approximately 500,000 tandem copies of an siRNA sequence that self-organized into a crystalline microsponge structure, which was highly resistant to degradation.

When mixed with small amounts of positively charged molecules (PEI) to increase cellular uptake, these siRNA microsponges were highly efficient at gene silencing. Indeed, just 1 picomole of PEI-associated microsponge siRNA induced a degree of silencing equivalent to that seen with 100 nanomole of siRNA associated with Lipofectamine, the polymer considered the “gold standard” for siRNA uptake efficiency, explains Hammond.

“The high density and large quantities of RNAs in [the microsponges] confer potential advantages in getting more RNA into the cell,” says Eric Kool of Stanford University in California, “and the method for making them is appealingly simple.” (Nature Materials, 11:316-22, 2012)


Lipofectamine Untested 1.5 pmole needed to deliver 1 nmole siRNA + charged lipids bind single RNA or DNA molecules None, toxic
Microsponges Remain stable up to 150°C 10 femtomoles needed to deliver 1 nmole siRNA siRNA repeats are further compacted with + charged PEI Gene delivery by direct infection into tumors, systemic delivery untested



































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