We have modified the CH3 domain interface of the antibody Fc region with selected mutations so that the engineered Fc proteins preferentially form heterodimers.These novel mutations create altered charge polarity across the Fc dimer interface such that co-expression of electrostatically matched Fc chains support favorable attractive interactions thereby promoting desired Fc heterodimer formation while unfavorable repulsive charge interactions suppress unwanted Fc homodimer formation.This new strategy allows the production of asymmetrical fusions base on Fc heterodimer where each chain is individually engineered to maximize functionality and selectivity of the fusion protein.