The present methods relate to generating nucleic acid molecules using non-natural nucleotides. In some methods, the nucleic acid molecules may be generated by hybridizing a plurality of oligonucleotides comprising one or more non-natural nucleotides and using a polymerase and/or a coupling agent to link the hybridized oligonucleotides. The methods also relate to the use of proximity effects to generate nucleic acid molecules using non-natural nucleotides. Furthermore, the methods relate to the use of at least one non-natural base in a DNA template in order to generate a replicate of the DNA template in which the non-natural base has been replaced with a natural base.