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Italy's highest court of appeal overturned the acquittal of US student Amanda Knox on Tuesday and ordered a retrial over the murder of her British housemate in what prosecutors said was a drug-fuelled sex attack.
Knox and her Italian former boyfriend Raffaele Sollecito -- originally sentenced to 26 and 25 years in prison for killing and sexually assaulting Meredith Kercher in 2007 -- were acquitted on appeal in 2011 after four years in prison.
Both now face a retrial in a Florence court after judges upheld a 2012 prosecution appeal against their acquittals.
Knox, 25, said the news was "painful" and insisted "the prosecution's theory of my involvement in Meredith's murder has been repeatedly revealed to be completely unfounded and unfair".
"No matter what happens, my family and I will face this continuing legal battle as we always have, confident in the truth and with our heads held high in the face of wrongful accusations and unreasonable adversity," she said in a statement.
Knox's lawyer Carlo Dalla Vedova told journalists outside the Rome courthouse that the Seattle student was upset but "willing to fight".
She said Knox has not yet decided whether she will turn up for the trial.
Kercher, 21, was found half-naked with her throat slashed in a pool of blood in her bedroom in the house in the university town of Perugia that she shared with Knox in November 2007.
Prosecutors had alleged that she was killed in a drug-fuelled sex attack, claiming Knox delivered the final blows while Sollecito and a third defendant held the victim down.
Investigators insist that 47 knife wounds on Kercher and the apparent use of two different knives in the attack meant that more than one killer had been involved.
Knox returned to the United States immediately after her release in 2011 and, should she not return to Italy, will likely be tried in absentia.
If convicted again, Italy may seek her extradition but the United States does not normally hand over its citizens for legal action.
Sollecito, who turned 29 on Tuesday, continued to protest his innocence.
"I am disappointed. But I am innocent and can go on with my head held high," lawyer Luca Maori quoted him as saying.
Prosecutors told the court Monday they were convinced the former lovers were guilty of murdering Kercher.
Calling for the judges to "make sure the final curtain does not drop on this shocking and dire crime," they said the acquittal, which was based mainly on the admissibility of DNA evidence, contained "omissions and many mistakes".
Prosecutor general Luigi Riello had described it as "a rare mix of violation of the law and illogicality."
The third accused, Ivory Coast-born drifter Rudy Guede, who has also denied the murder, is the only person still in prison for the crime.
Kercher family lawyer Francesco Maresca punched the air in victory at the court decision.
"This decision serves to review the definitive and final truth of Meredith's murder. Guede was not alone, the judges will tell us who was there with him," he said.
Kercher's older sister Stephanie said her family welcomed the ruling.
There are "still questions that are unanswered and we are all looking to find out the truth," she told Sky News.
The key to the appeal was an independent analysis of two pieces of evidence that had helped convict Knox and Sollecito -- a kitchen knife and Kercher's bra clasp.
An appeals judge quashed the 2009 convictions of Knox and Sollecito in 2011 after the review cast serious doubt on the original analysis, with experts and video evidence pointing to sloppy practice among the police at the crime scene and possible contamination of evidence.
"The court of appeal in Florence will very likely look at all the evidence again, from scratch, possibly calling in new external DNA experts," said criminology professor Ernesto Savona.
Knox has been repeatedly painted by her accusers as a seductive "she-devil" who had an unhealthy obsession with sex, while her defence has insisted she is simply a naive girl-next-door, a yoga lover whose nickname "Foxy Knoxy" referred to her childhood football skills.
In her first interrogation following the murder, Knox said that she was in the house at the time, and falsely identified the owner of a bar where she worked as a waitress as the killer.
She later said she was with Sollecito at his house all night and blamed her initial comments on exhaustion and police coercion.
On Tuesday, she expressed sympathy for Kercher's family, saying "our hearts go out to them."