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Xu, Y., Tokar, E

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A reduction in expression of mR A administered as part of a repeat-dose regimen, wherein the level of protein translated from the administered R A is reduced by more than 40% in comparison to another dose within the repeat-dose regimen is referred to herein as "repeat-dose resistance." Properties of the Pharmaceutical Compositions [0001790] The pharmaceutical compositions described herein can be characterized by one or more of the following properties: Bioavailability [0001791] The polynucleotides or compositions when formulated into a composition with a delivery agent as described herein, can exhibit an increase in bioavailability as compared to a composition lacking a delivery agent as described herein