In various aspects and embodiments the invention provides methods and reagents for controlling gene expression, and for treating disorders and diseases. Embodiments provide methods and reagents specifically for the regulation of MLCK expression and for the use thereof in treating disorders and diseases. Various embodiments provide methods and reagents for specifically down regulating the expression of MLCK-L more efficiently than that of MLCK-S, and for the use thereof in treating disorders and diseases. Embodiments provide siNA for the same, particularly siRNAs. Various of the embodiments are useful for the treatment of inflammatory disorders and diseases, including, for one example in this regard, Asthma.