On Friday, Italian forensic experts began tests on the crucial - and previously untested - piece of DNA found on the alleged murder weapon.
Defense lawyer Ted Simon tells ABC News that preliminary findings have found no trace of Kercher's DNA on the knife.
"The findings were Meredith Kercher was not on the blade - something that the prosecution was hoping for," says Simon. "Those hopes have been dashed."
The new findings could refute the prosecution's claim that the knife was used to kill Kercher.
"These are reliable findings," says Simon. However, he cautioned that the findings remain unofficial until submitted to the court.
It was the latest twist in the long-running legal drama that began in November 2007 after Kercher was found stabbed to death in the home she shared with Knox in Perugia, Italy, where both were studying abroad.
Knox, now 26, of Seattle, was arrested, along with her then-boyfriend, Raffaele Sollecito. Both Knox and Sollecito denied any involvement, saying they weren't in the apartment at the time. Nevertheless, both were initially convicted of the crime and sentenced to long prison terms.
A Perugia appeals court acquitted them in 2011, criticizing virtually the entire case mounted by prosecutors. But in March, Italy's supreme court ordered a new third trial for Knox and her former Italian boyfriend.
Knox has remained in Seattle during the trial while her legal team mounts a defense. Even though she is not there, Knox says she is still haunted by the 1,400 nights she spent locked in an Italian prison.
A young man from Ivory Coast, Rudy Guede, was convicted of the slaying in a separate proceeding and is serving a 16-year sentence.