We show that the dosed administration of siRNA PMP22-SQ NPs normalizes the expression of Schwann cell-specific PMP22 in two preclinical CMT1A mouse models, without an off-target effect on P0 or MBP, re-establishes electrophysiological activity of both motor and sensory nerves and results in the rapid recovery of locomotor functions and muscular strength of the limbs. Here, MBP is linked to Charcot-Marie-Tooth disease type 1A.