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Knox and Raffaele Sollecito were convicted in 2009 of killing 21-year-old British student Meredith Kercher in what was described as a drug-fuelled sexual assault.
The retrial of American Amanda Knox and her former Italian boyfriend for the 2007 murder of Meredith Kercher opened in Florence on Monday but neither of the accused were in court for the first hearing.
Knox and Raffaele Sollecito were convicted in 2009 of killing 21-year-old British student Meredith Kercher in what was described as a drug-fuelled sexual assault.
After winning an appeal in 2011 quashing the guilty verdict, both were freed from prison.
But a new appeals process has begun after Italy's supreme court overturned the acquittals in March, citing "contradictions and inconsistencies".
Sollecito's father Francesco said on Monday he was confident his son's innocence would be confirmed.
"Deeper examination can only demonstrate what we already know, that is that Raffaele Sollecito has nothing to do with what that poor girl had to suffer," he told reporters.
Knox, 26, has always denied murdering Kercher, when both were university exchange students in Perugia.
She told U.S. television this month that "common sense" told her not to return to Italy for the retrial.
"I was imprisoned as an innocent person and I just can't re-live that," she told NBC television.
Knox is not obliged to attend and can be represented by her lawyers, who said she was following the case closely from home in Seattle.
If found guilty, she could appeal again to Italy's supreme court. If that failed, Italy could request her extradition.
Sollecito, 29, who has also always protested his innocence, plans to attend some of the hearings, his father said. Kercher was found with more than 40 wounds, including a deep gash in the throat, in the apartment she shared with Knox in Perugia, a picturesque town in central Italy's Umbria region that attracts students from around the world.
Lawyers for Kercher's family have welcomed the retrial, criticising the previous ruling as "superficial".
Knox has said in recent interviews she wants to visit Kercher's grave, but the Leeds University student's family said in a statement at the weekend that the grave was Meredith's "safe place" and that they hoped "that is respected by all".
Francesco Maresca, a lawyer for the Kercher family, said the supreme court's decision to throw out the acquittals reinforced signs of Knox and Sollecito's guilt.
"We have always mantained that they are guilty and that they were present at the crime scene," he said.
Referred to by the nickname "Foxy Knoxy" in many tabloid headlines, Knox was initially portrayed as a sex-obsessed she-devil by prosecutors but a lobbying campaign by her family helped modify perceptions.
In a memoir published this year, she painted herself as a naive young woman and a victim of Italy's snail-paced justice system, which drew heavy criticism for its handling of the case.
In explaining its decision to overturn the acquittal of Knox and Sollecito, the supreme court said the appeals court that freed them had not taken all the evidence into consideration.
It said the one person still in jail for the murder, Ivory Coast-born Rudy Guede, who is serving a 16-year sentence, was unlikely to have committed the crime alone.
Prosecutors said Kercher was held down and stabbed after she resisted attempts by Knox, Sollecito and Guede to involve her in an orgy.
The supreme court said the theory of a sex game that spiralled out of control should be re-examined.
The prosecution's case was weakened in the last trial by forensic experts who undermined the credibility of DNA evidence provided by police and sharply criticised their initial response procedures at the scene of the killing.
(Editing by Gareth Jones)
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