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Issue 44, 2018
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Barcoding chemical modifications into nucleic acids improves drug stability in vivo

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Abstract

The efficacy of nucleic acid therapies can be limited by unwanted degradation. Chemical modifications are known to improve nucleic acid stability, but the (i) types, (ii) positions, and (iii) numbers of modifications all matter, making chemically optimizing nucleic acids a combinatorial problem. As a result, in vivo studies of nucleic acid stability are time consuming and expensive. We reasoned that DNA barcodes could simultaneously study how chemical modification patterns affect nucleic acid stability, saving time and resources. We confirmed that rationally designed DNA barcodes can elucidate the role of specific chemical modifications in serum, in vitro and in vivo; we also identified a modification pattern that enhanced stability. This approach to screening chemical modifications in vivo can efficiently optimize nucleic acid structure, which will improve biomaterial-based nucleic acid drugs.

Graphical abstract: Barcoding chemical modifications into nucleic acids improves drug stability in vivo

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Publication details

The article was received on 21 Jun 2018, accepted on 10 Aug 2018 and first published on 28 Aug 2018


Article type: Paper
DOI: 10.1039/C8TB01642A
J. Mater. Chem. B, 2018,6, 7197-7203
  • Open access: Creative Commons BY license
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    Barcoding chemical modifications into nucleic acids improves drug stability in vivo

    C. D. Sago, S. Kalathoor, J. P. Fitzgerald, G. N. Lando, N. Djeddar, A. V. Bryksin and J. E. Dahlman, J. Mater. Chem. B, 2018, 6, 7197
    DOI: 10.1039/C8TB01642A

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