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Definitely. 49ers have had a lot of success there in recent years though. They are undefeated against the Seahawks since Geno Smith took over as QB. We will see, 49ers definitely don't look like themselves and Seattle really needs a win too after dropping two in a row.
MacDonald's defensive scheme looked awful good against the 49ers last year when he was with the Ravens. I don't think he has the same caliber players with Seattle but he might be able to give them fits.