For xDNA to be used as a substitute structure for information storage, it requires a reliable replication mechanism. Research into xDNA replication using a Klenow fragment from DNA polymerase I shows that a natural base partner is selectively added in instances of single-nucleotide insertion. However, DNA polymerase IV (Dpo4) has been able to successfully use xDNA for these types of insertions with high fidelity, making it a promising candidate for future research in extending replicates of xDNA. xDNA's mismatch sensitivity is similar to that of B-DNA.