A mission took place in 21 BBY on Serenno after Darth Sidious ordered his apprentice, Count Dooku, to kill Asajj Ventress. After Ventress survived Dooku's assassination attempt, she sought revenge by going to her fellow Nightsisters for aid. Taking Karis and Naa'leth to Serenno, Ventress attempted to assassinate Dooku, but the Sith Lord repelled the attack, defeating his assailants.
The Nightsisters believe they have Dooku at their mercy
Asajj Ventress and her two Nightsisters became invisible and infiltrated Tyranus's palace. Ventress shot a poison dart into Dooku's neck that blinded him, although he could still sense them through the Force and mistook them as Jedi. Nontheless, the Count stated that he did not rely on eyesight alone to detect them. With that, Dooku attacked Ventress in a sudden flip jump, beginning a lightsaber duel in the Count's bedroom. The other two Nightsisters joined in on the fight when they could, however, the expertise and fluid bladework of the Count kept them separated. Ventress and another went on the offensive while Dooku held a tight defensive through the corridor until eventually it lead into his office. By this point, Dooku was forced between the three at once in his office and despite his efforts was quickly draining his stamina against three opponents at once. Ventress, who had managed to stay disguised during the entire confrontation, managed to disarm the Sith Lord by Force pushing him into his desk and was about to strike the killing blow, but Dooku, feigning exhaustion and vulnerability, defended himself by striking Ventress and her accomplices with Force lightning, throwing them out the window and over a cliff, ending the attack. However, the three Nightsisters survived and returned to Dathomir.
Due to his attackers' use of Jedi lightsabers, Tyranus mistakenly believed that the Jedi had tried to assassinate him. Wishing to protect himself, he sought a new apprentice to replace Ventress (whom he erroneously believed to be dead).
Given the failure of their direct attempt to kill Tyranus, the Nightsisters developed a new plot to kill the Sith Lord using a double agent. To arrange the plan, Mother Talzin contacted Tyranus, offering to provide one of the Nightbrothers to be his new assassin. Tyranus, seeing this as an opportunity to get the new apprentice he desired, agreed. After selecting Savage Opress to be their pawn, Talzin presented the hulking Zabrak to Tyranus, who was pleased with his new warrior, unaware of his true loyalties.
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