Yale University's biomedical engineers have hit upon a workable possbilility that may help stop HIV infection in the future - where nanoparticles can be used as a safe measure to deliver potentially therapeutic RNAs into vaginal cells.
Led by Mark Saltzman, the researchers believe that similar particles could be used to make topical creams containing anti-HIV RNAs.
AdvertisementThe team wanted to find a better way to deliver short interfering RNAs (siRNAs) into vaginal cells that might come into contact with HIV.
These short snippets of RNA can be designed to repress specific genes, and siRNAs against HIV genes have been shown to stop the virus reproducing in humanized mice.
Usually, siRNAs are transferred into cells by attaching them to lipids, which is expensive and can be toxic, reports Nature.
In the new study, however, the scientists instead found a surprisingly simple way to pack thousands of siRNAs into nano-sized bits of a biodegradable and biocompatible plastic that is already approved for medical uses.
Such nanoparticles could then be incorporated into a vaginal gel, which could be applied by women before sex to help prevent infection.
"It's surprising that you can load as much siRNA as you can into particles like this. It wasn't obvious that it would work," said Saltzman.
For developing the new method, the team first mixed the siRNA molecules with spermidine - a natural condensing agent, which formed the siRNA into clumps that were later encapsulated in porous plastic particles 100 nanometres across.
Some siRNAs are known to stop the HIV virus replicating, and thus the researchers tested this delivery technique in mice using siRNA that 'silences' or prevents the production of a green fluorescent protein (EGFP).
After transferring the loaded nanoparticles into the vaginas of female mice engineered to produce EGFP, the team could easily see how well their 'medicine' worked by checking if the vaginal cells stopped fluorescing.
The nanoparticle-delivery system silenced fluorescence just as well as a traditional lipid delivery system.
But, the researchers found that the lipid-treated mice developed signs of vaginal irritation, whereas those given the nanoparticles did not.
The nanoparticles also did a good job of spreading siRNA around - deep into vaginal tissue and into the uterus - and released their cargo slowly over a month.
And now, Saltzman is testing his nanoparticles against the monkey version of HIV, and says it "looks good". But there's still a long way to go.
"The challenge is to show it works against disease," he said.
The study is published in Nature Materials.
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