Barcoding chemical modifications into nucleic acids improves drug stability in vivo

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...

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Bibliographic Details
Published in:Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2018-11, Vol.6 (44), p.7197-723
Main Authors: Sago, Cory D, Kalathoor, Sujay, Fitzgerald, Jordan P, Lando, Gwyneth N, Djeddar, Naima, Bryksin, Anton V, Dahlman, James E
Format: Article
Language:English
Subjects:
Acids
Bar codes
Biomaterials
Biomedical materials
Chemical modification
Chemistry
Combinatorial analysis
Deoxyribonucleic acid
DNA
Gene sequencing
In vivo methods and tests
Nucleic acids
Optimization
Organic chemistry
Stability
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Summary: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. The efficacy of nucleic acid therapies can be limited by unwanted degradation.
ISSN:2050-750X
2050-7518
DOI:10.1039/c8tb01642a