Other Zika vaccines in the works use either a virus or DNA to get into cells.
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However, the Penn team uses RNA - a molecule that acts as a messenger in cells.
It's much more efficient than DNA in getting into cells.
"If you inject DNA, you find about 1 in 100 cells actually take it up. When you inject RNA, 80, 90-plus percent of the cells take it up. So it's much more efficient," said Dr. Drew Weissman.
In lab animals, it only took one dose - and a much smaller dose - to create immunity.
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That would make it much easier to vaccinate big populations, especially in developing nations where it could be hard to get people back for a second dose.
Penn's vaccine may also be substantially cheaper and faster to produce.
Human trials could begin in 12 to 18 months.