Enzymatic DNA synthesis for digital information storage.
Open accessAbstract
DNA is an emerging storage medium for digital data but its adoption is hampered by limitations of phosphoramidite chemistry, which was developed for single-base accuracy required for biological functionality. Here, we establish a de novo enzymatic DNA synthesis strategy designed from the bottom-up for information storage. We harness a template-independent DNA polymerase for controlled synthesis of sequences with user-defined information content. We demonstrate retrieval of 144-bits, including addressing, from perfectly synthesized DNA strands using batch-processed Illumina and real-time Oxford Nanopore sequencing. We then develop a codec for data retrieval from populations of diverse but imperfectly synthesized DNA strands, each with a ~30% error tolerance. With this codec, we experimentally validate a kilobyte-scale design which stores 1 bit per nucleotide. Simulations of the codec support reliable and robust storage of information for large-scale systems. This work paves the way for alternative synthesis and sequencing strategies to advance information storage in DNA.
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Terminator-free TdT-based DNA synthesis was proved to be a superior combination with Nanopore sequencer, which is optimal for sequencing long DNA strands with high error rate.
“It is worth mentioning that, in the study by Lee et al. (2019), the terminator free TdT-based DNA synthesis was proved to be a superior combination with Nanopore sequencer which is optimal for sequencing of long DNA strands with high error rate.”
From Large-Scale de Novo Oligonucleotide Synthesis for Whole-Genome Synthesis and Data Storage: Challenges and Opportunities (2021) · cites this paper as Lee et al., 2019
TdT-based enzymatic DNA synthesis has already been applied to data storage applications.
“Indeed, two groups of Jensen et al. (2018) and Lee et al. (2018) have already applied TdT-based enzymatic DNA synthesis method to data storage applications.”
From Large-Scale de Novo Oligonucleotide Synthesis for Whole-Genome Synthesis and Data Storage: Challenges and Opportunities (2021) · cites this paper as Lee et al., 2018
Recent progress in nucleic acid synthesis and sequencing continues to reduce the cost of writing and reading DNA, foreshadowing future commercially competitive DNA-based information storage.
“Recent progress in nucleic acid synthesis and sequencing technologies continue to reduce the cost of writing and reading DNA, foreshadowing future commercially competitive DNA-based information storage1,3–5.”
From Random access DNA memory using Boolean search in an archival file storage system (2021) · cites this paper as [5]
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Self-citation
- Authors
- Lee, H. H., Kalhor, R., Goela, N., Bolot, J., & Church, G. M.
- Affiliations
- Harvard University (US)
- Corresponding author
- Lee, Henry H.
- Church, George M.
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2018-06-16
- Volume
- 10
- Issue
- 1
- Pages
- 2383-2383
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6546792
- OpenAlex
- W2947129118
- Cited by
- 265
- References
- 51
- Citations by year
- 2026: 30 · 2025: 39 · 2024: 48 · 2023: 38 · 2022: 29 · 2021: 35 · 2020: 31 · 2019: 13 · 2018: 2
- FWCI
- 8.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- U.S. Department of Energy (DE‐FG02‐, DEFG0202ER63445, FG02-02ER63445, Grant DE-FG02-02ER63445)
- U.S. Department of Health and Human Services (R01-MH103910-02)
- National Institutes of Health (DE-FG02-02ER63445)
- National Institute of Mental Health (R01MH103910)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Biological Computing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- DNA data storage, enzymatic DNA synthesis, terminal deoxynucleotidyl transferase, apyrase, nanopore sequencing
- MeSH terms
- Apyrase, DNA, DNA Nucleotidylexotransferase, Information Storage and Retrieval, Sequence Analysis, DNA, Nanopores
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