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Design and enhanced gene silencing activity of spherical 2′-fluoroarabinose nucleic acids (FANA-SNAs)

Drug delivery vectors for nucleic acid therapeutics (NATs) face significant barriers for translation into the clinic. Spherical nucleic acids (SNAs) – nanoparticles with an exterior shell made up of DNA strands and a hydrophobic interior – have recently shown great potential as vehicles to improve t...

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Autores principales: Fakih, Hassan H., Katolik, Adam, Malek-Adamian, Elise, Fakhoury, Johans J., Kaviani, Sepideh, Damha, Masad J., Sleiman, Hanadi F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179377/
https://www.ncbi.nlm.nih.gov/pubmed/34164068
http://dx.doi.org/10.1039/d0sc06645a
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author Fakih, Hassan H.
Katolik, Adam
Malek-Adamian, Elise
Fakhoury, Johans J.
Kaviani, Sepideh
Damha, Masad J.
Sleiman, Hanadi F.
author_facet Fakih, Hassan H.
Katolik, Adam
Malek-Adamian, Elise
Fakhoury, Johans J.
Kaviani, Sepideh
Damha, Masad J.
Sleiman, Hanadi F.
author_sort Fakih, Hassan H.
collection PubMed
description Drug delivery vectors for nucleic acid therapeutics (NATs) face significant barriers for translation into the clinic. Spherical nucleic acids (SNAs) – nanoparticles with an exterior shell made up of DNA strands and a hydrophobic interior – have recently shown great potential as vehicles to improve the biodistribution and efficacy of NATs. To date, SNA design has not taken advantage of the powerful chemical modifications available to NATs. Here, we modify SNAs with 2′-deoxy-2′-fluoro-d-arabinonucleic acid (FANA-SNA), and show increased stability, enhanced gene silencing potency and unaided uptake (gymnosis) as compared to free FANA. By varying the spacer region between the nucleic acid strand and the attached hydrophobic polymer, we show that a cleavable DNA based spacer is essential for maximum activity. This design feature will be important when implementing functionalized nucleic acids into nanostructures for gene silencing. The modularity of the FANA-SNA was demonstrated by silencing two different targets. Transfection-free delivery was superior for the modified SNA compared to the free FANA oligonucleotide.
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spelling pubmed-81793772021-06-22 Design and enhanced gene silencing activity of spherical 2′-fluoroarabinose nucleic acids (FANA-SNAs) Fakih, Hassan H. Katolik, Adam Malek-Adamian, Elise Fakhoury, Johans J. Kaviani, Sepideh Damha, Masad J. Sleiman, Hanadi F. Chem Sci Chemistry Drug delivery vectors for nucleic acid therapeutics (NATs) face significant barriers for translation into the clinic. Spherical nucleic acids (SNAs) – nanoparticles with an exterior shell made up of DNA strands and a hydrophobic interior – have recently shown great potential as vehicles to improve the biodistribution and efficacy of NATs. To date, SNA design has not taken advantage of the powerful chemical modifications available to NATs. Here, we modify SNAs with 2′-deoxy-2′-fluoro-d-arabinonucleic acid (FANA-SNA), and show increased stability, enhanced gene silencing potency and unaided uptake (gymnosis) as compared to free FANA. By varying the spacer region between the nucleic acid strand and the attached hydrophobic polymer, we show that a cleavable DNA based spacer is essential for maximum activity. This design feature will be important when implementing functionalized nucleic acids into nanostructures for gene silencing. The modularity of the FANA-SNA was demonstrated by silencing two different targets. Transfection-free delivery was superior for the modified SNA compared to the free FANA oligonucleotide. The Royal Society of Chemistry 2021-01-15 /pmc/articles/PMC8179377/ /pubmed/34164068 http://dx.doi.org/10.1039/d0sc06645a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Fakih, Hassan H.
Katolik, Adam
Malek-Adamian, Elise
Fakhoury, Johans J.
Kaviani, Sepideh
Damha, Masad J.
Sleiman, Hanadi F.
Design and enhanced gene silencing activity of spherical 2′-fluoroarabinose nucleic acids (FANA-SNAs)
title Design and enhanced gene silencing activity of spherical 2′-fluoroarabinose nucleic acids (FANA-SNAs)
title_full Design and enhanced gene silencing activity of spherical 2′-fluoroarabinose nucleic acids (FANA-SNAs)
title_fullStr Design and enhanced gene silencing activity of spherical 2′-fluoroarabinose nucleic acids (FANA-SNAs)
title_full_unstemmed Design and enhanced gene silencing activity of spherical 2′-fluoroarabinose nucleic acids (FANA-SNAs)
title_short Design and enhanced gene silencing activity of spherical 2′-fluoroarabinose nucleic acids (FANA-SNAs)
title_sort design and enhanced gene silencing activity of spherical 2′-fluoroarabinose nucleic acids (fana-snas)
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179377/
https://www.ncbi.nlm.nih.gov/pubmed/34164068
http://dx.doi.org/10.1039/d0sc06645a
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