The present disclosure provides multiparametric codon optimization methods to improve at least a property in a candidate nucleic acid sequence. Such parameters include improving nucleic acid stability (e.g., mRNA stability), increasing translation efficacy in the target tissue, reducing the number of truncated proteins expressed, improving the folding or prevent misfolding of the expressed proteins, reducing toxicity of the expressed products, reducing cell death caused by the expressed products, and increasing or decreasing protein aggregation. After such optimization, the resulting optimized nucleic acid sequence has at least one optimized property with respect to the candidate nucleic acid sequence.
