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Gold Nanoparticles Help With Gene Knockdowns
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.
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| 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. |
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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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