May 26, 2006

Gold Nanoparticles Help With Gene Knockdowns

graphic of a gene In a gene "knock down," an antisense DNA strand pairs with a matching mRNA sequence, neutralizing the mRNA. Gold nanoparticles make the antisense DNA more stable and effective.

Researchers have been exploring the potential of a technique called antisense for more than 20 years. Antisense molecules "knock down" or neutralize the effects of particular genes and thus are useful tools in the laboratory. They may also have potential for treating diseases like cancer and AIDS, where knocking down the activity of a particular gene might be an effective therapy. However, researchers have faced several technical challenges working with antisense molecules, starting with getting them into cells. Investigators from Northwestern University have now used gold nanoparticles to deliver antisense molecules into cells — and found that they become more effective once they're inside.

Not all genes are turned on or "expressed" at once. Each gene's expression is carefully controlled by the cell. When it's time for a cell to make proteins from a particular gene, it copies the gene's DNA sequence into matching messenger RNA (mRNA) molecules. The sequences in those mRNAs are then used by the cell to make proteins. Antisense molecules are stretches of DNA that researchers design to pair with particular mRNA sequences. When the antisense molecules bind their target mRNAs, the mRNAs are essentially neutralized.

For the last ten years, researchers at Northwestern University have been studying the properties of DNA strands bound to the surface of gold nanoparticles. Recently, they found that they're more stable and bind target sequences more effectively than identical sequences that aren't bound to gold nanoparticles. The research team, working with support from a NIH Director's Pioneer Award and from NIH's National Cancer Institute, reasoned that, given their unique properties, gold nanoparticles could potentially be a good agent for delivering antisense DNA into cells. They attached multiple strands of antisense DNA to the surface of each gold nanoparticle to create "antisense nanoparticles." They then tested the nanoparticles in mouse cells with a gene for a protein that causes the cells to illuminate under a microscope when light of a certain wavelength shines on them.

The researchers report in the May 19, 2006, issue of the journal Science that they were able to tune the amount of gene expression within the cells by controlling the amount of DNA attached to the gold nanoparticles. When compared to other antisense agents that are available, the nanoparticles were more stable and could bind to target mRNAs more effectively. Over 99% were taken up by the mouse cells, yet they didn't seem to be toxic to them.

Future plans include trying to target the new antisense nanoparticles to specific cell types or even different components within cells. The researchers speculate that antisense nanoparticles might have potential for clinical use one day, by knocking down the expression of errant genes that are causing disease.

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