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In an astonishing legal about-turn, Italy's highest appeal court on Tuesday quashed the acquittal of US student Amanda Knox over the sexual assault and brutal murder of her British housemate in 2007 and ordered a retrial.
Knox and her Italian former boyfriend Raffaele Sollecito -- originally sentenced to 26 and 25 years in prison for killing Meredith Kercher -- were acquitted on appeal in 2011 after four years behind bars.
Both now face a retrial in a Florence court after judges upheld a prosecution appeal against their acquittals, although no date has yet been set.
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".
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 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 will likely be tried in absentia. If she is convicted definitively, 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, saying he would "carry on with my head held high".
Prosecutors called on the court Monday to "make sure the final curtain does not drop on this shocking and dire crime," saying the acquittal 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 after experts and video evidence pointed to sloppy practice among the police at the crime scene and possible contamination of evidence.
On Monday, Riello lashed out at the appeal judges for assuming evidence had been contaminated when it suited the defendants, but placing their faith in the DNA proof when it pointed to Guede's guilt.
Lawyer Giulia Bongiorno insisted forensic police had committed "grave errors", including not bagging a bra clasp later used as key evidence until 47 days after the murder, when photographs of the crime scene showed it had been moved.
Knox has been repeatedly painted by her accusers as a seductive "she-devil", while her defence has insisted she is simply a naive girl-next-door.
She maintains she came home after the murder to find there had been what she thought was a break-in. She dismissed blood in the bathroom for menstrual blood and showered before reporting the suspected burglary.
"Of all the things that Amanda did that day, nothing attracted more criticism than her failure to raise the alarm as soon as she saw so many things out of place," wrote Sollecito in his 2012 memoir.
"It wasn't just the police who... could not fathom how she could go ahead with her shower after finding blood on the tap, much less put her wet feet on the bath mat, which was also stained, and drag it across the floor," he said.