The gang of three broke into the museum archives building in Dublin late on Wednesday, tied up a security guard and loaded four rhino heads -- each with two horns --- onto a van, police said.
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The guard, who was unhurt, eventually freed himself and raised the alarm, but not before the thieves had made off with their haul.
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Rhino horns have become increasingly valuable as a component of traditional medicines in Asia, where they are falsely believed to have powerful healing properties.
Poachers feeding the lucrative market have decimated rhino populations across Africa -- in South Africa, more than 200 of the animals have been killed so far this year.
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A spokeswoman for the Irish museum said fears about a possible theft had prompted curators to move the horns from public display last year into storage.
"Their price is based on weight and the total amount stolen could have a street value in the region of 500,000 euros," she said.
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Police said they had begun an investigation into the theft, adding: "The crime scene is sealed off for forensic technical examination."
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