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MIT uses tiny spheres to target cancer

Mon, 02/27/2012 - 10:41am
Mass High Tech: The Journal of New England Technology

MIT scientists say tiny, sponge-like spheres may more efficiently deliver RNA interference-based treatments to patients suffering from cancer and other diseases.

 

RNA interference is a phenomenon that can shut off malfunctioning genes with short snippets of RNA, but it has been challenging to find a way to efficiently deliver the RNA, according to the scientists, who published their new system in the Feb. 26 issue of Nature Materials.

 

Short interfering RNA (siRNA), which are used for RNA interference, are broken down quickly in the body by enzymes defending against infection by RNA viruses.

 

“It’s been a real struggle to try to design a delivery system that allows us to administer siRNA, especially if you want to target it to a specific part of the body,” MIT Engineering Professor Paula Hammond explained in a statement.

 

She and her colleagues developed a new delivery method in which RNA is packed into microspheres dense enough to withstand degradation until they reach their destinations. The new system knocks down expression of specific genes as effectively as existing delivery methods, they claimed, and with a much smaller dose of particles.

 

Hammond said the particles may be used to treat cancer and other chronic diseases caused by a misbehaving gene. “RNA interference holds a huge amount of promise for a number of disorders, one of which is cancer, but also neurological disorders and immune disorders,” she said.

 

RNA interference, discovered in 1998, occurs naturally. It allows cells to fine-tune their genetic expression. Genetic information is normally carried from DNA in the nucleus to ribosomes, cellular structures where proteins are made. The siRNA binds to the messenger RNA that carries the genetic information, destroying instructions before they reach the ribosome.

 

Scientists are working on many ways to artificially replicate this process to target specific genes, including packaging siRNA into nanoparticles made of lipids or inorganic materials such as gold. Though many of those have shown some success, the researchers said it’s difficult to load large amounts of siRNA onto those carriers, because the short strands do not pack tightly.

 

Hammond’s team instead packaged the RNA as one long strand that would fold into a tiny, compact sphere. The researchers tested the spheres by programming them to deliver RNA sequences that shut off a gene that causes tumor cells to glow in mice. They found that they could achieve the same level of gene knockdown as conventional nanoparticle delivery, but with about one-thousandth as many particles. The microsponges accumulate at tumor sites because the blood vessels surrounding tumors are leaky (they have tiny pores through which very small particles can squeeze).

 

Going forward, the researchers plan to design microspheres coated with polymers that specifically target tumor or other diseased cells. They are also working on spheres that carry DNA for potential use in gene therapy.

 

Once the spheres formed, the researchers wrapped them in a layer of positively charged polymer, which induces the spheres to pack even more tightly and helps them to enter cells. After the spheres enter a cell, the Dicer enzyme chops the RNA at specific locations, releasing the 21-nucleotide siRNA sequences.

 

The researchers tested the spheres by programming them to deliver RNA sequences that shut off a gene that causes tumor cells to glow in mice. They found that they could achieve the same level of gene knockdown as conventional nanoparticle delivery, but with about one-thousandth as many particles. The microsponges accumulate at tumor sites because the blood vessels surrounding tumors are leaky: they have tiny pores through which very small particles can squeeze.

 

Going forward, the researchers plan to design microspheres coated with polymers that specifically target tumor or other diseased cells. They are also working on spheres that carry DNA for potential use in gene therapy.

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