Methods for encoding data in synthetic DNA include, for an input data sequence, constructing a codebook of a number of unique codewords, of a nucleotide length, which are constructed such that, for each codeword, the codeword is formed from a selection of nucleotide pairs from a first predefined dictionary of nucleotide pairs, and, if the nucleotide length of the codeword is odd, an additional selection of a nucleotide from a second predefined dictionary of individual nucleotides. For each symbol from the input data sequence, at least one codeword is designated as associable therewith, and each symbol is coded as one codeword selected from the designated at least one codeword associable with that symbol. A code is formed from the codewords, arranged in corresponding order to that of their respective symbols in the input data sequence. A DNA sequence is synthetized with nucleotides ordered to match the code.