Issue 44, 2018

Barcoding chemical modifications into nucleic acids improves drug stability in vivo

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

Article information

Article type
Paper
Submitted
21 jun 2018
Accepted
10 aug 2018
First published
28 aug 2018
This article is Open Access
Creative Commons BY license

J. Mater. Chem. B, 2018,6, 7197-7203

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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