Advances and challenges in non-canonical nucleic acids data storage.

Abstract

Canonical nucleic acids (DNA and RNA) naturally store genetic information with high density and programmability, making them promising candidates for molecular data storage. However, their susceptibility to degradation under harsh conditions, such as extreme pH, nuclease activity, and chemical attack, limits practical applications. In contrast, non-canonical nucleic acids (ncNAs) with natural or synthetic structural modifications exhibit enhanced stability and unique functional potential. This review systematically summarizes the fundamental properties of ncNAs, evaluates their suitability for molecular data storage, and discusses how their distinctive advantages may overcome the intrinsic limitations of canonical nucleic acids while addressing challenges in next-generation storage systems.