Authors
Xinyu Sun, Yufeng Pei, Pan Tan, Tianyuan Bian, Ruoyu Wang, Yan Wang, Jiacheng Xie, Liang Hong, Jie Song
Published in
Science advances. Volume 12. Issue 26. Pages eaed2917. Jun 26, 2026. Epub Jun 24, 2026.
Abstract
DNA is a promising medium for data storage due to its high density and low energy cost. Long-stranded DNA with minimal indexing improves storage density but suffers from poor stability. To address this, we introduce a long-stranded xeno nucleic acid-circular single-stranded DNA (XNA-cssDNA) hybrid strategy to enhance storage robustness. We evaluated multiple XNAs under extreme conditions and identified 2'-fluoro-arabinonucleic acid (FANA) as the optimal storage material. To overcome XNA synthesis length and speed limitations, we used a temperature-guided language model to evolve a FANA polymerase Tgomut, which is ~4.4-fold faster than TgoD4K and enables synthesis of strands exceeding 7500 nucleotides. Data-encoded cssDNA were produced using M13 bacteriophage. The resulting FANA-cssDNA hybrids show strong resistance to chemical and enzymatic degradation. Using a dual-strategy framework, we achieved reliable data writing and reading with 100% data recovery, even after DNA degradation, and successfully visualized encoded digital data and an enhanced green fluorescent protein gene in mammalian cells.
PMID:
42341119
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.
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