The invention relates to compositions and methods for cMLCK gene transfer. In some aspects, the invention provides compositions and methods for treating advanced heart failure in a subject by cMLCK gene transfer, in particular, by administering to a subject an effective amount of a polynucleotide vector that encodes a cMLCK protein, expressing the cMLCK protein from the polynucleotide vector in the heart cells of the subject, and improving ventricular function of the heart. In other aspects, the invention provides compositions and methods for expressing a cMLCK protein in a subject, in particular, by administering to a subject a polynucleotide vector that encodes the cMLCK protein and expressing the cMLCK protein from the polynucleotide vector in the heart cells of the subject, wherein the subject has advanced heart failure.
