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Glutaraldehyde Cross-Linking of Oligolysines Coating DNA Origami Greatly Reduces Susceptibility to Nuclease Degradation.
Anastassacos, Frances M; Zhao, Zhao; Zeng, Yang; Shih, William M.
Afiliación
  • Anastassacos FM; Department of Cancer Biology , Dana-Farber Cancer Institute , Boston , Massachusetts 02215 , United States.
  • Zhao Z; Wyss Institute for Biologically Inspired Engineering at Harvard , Boston , Massachusetts 02115 , United States.
  • Zeng Y; Department of Cancer Biology , Dana-Farber Cancer Institute , Boston , Massachusetts 02215 , United States.
  • Shih WM; Department of Biological Chemistry and Molecular Pharmacology , Harvard Medical School , Boston , Massachusetts 02115 , United States.
J Am Chem Soc ; 142(7): 3311-3315, 2020 02 19.
Article en En | MEDLINE | ID: mdl-32011869
DNA nanostructures (DNs) have garnered a large amount of interest as a potential therapeutic modality. However, DNs are prone to nuclease-mediated degradation and are unstable in low Mg2+ conditions; this greatly limits their utility in physiological settings. Previously, PEGylated oligolysines were found to protect DNs against low-salt denaturation and to increase nuclease resistance by up to ∼400-fold. Here we demonstrate that glutaraldehyde cross-linking of PEGylated oligolysine-coated DNs extends survival by up to another ∼250-fold to >48 h during incubation with 2600 times the physiological concentration of DNase I. DNA origami with cross-linked oligolysine coats are non-toxic and are internalized into cells more readily than non-cross-linked origami. Our strategy provides an off-the-shelf and generalizable method for protecting DNs in vivo.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polilisina / ADN / Glutaral / Reactivos de Enlaces Cruzados / Desoxirribonucleasa I Límite: Humans Idioma: En Revista: J Am Chem Soc Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polilisina / ADN / Glutaral / Reactivos de Enlaces Cruzados / Desoxirribonucleasa I Límite: Humans Idioma: En Revista: J Am Chem Soc Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos