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Sequence-responsive unzipping DNA cubes with tunable cellular uptake profiles

Sequence-responsive unzipping DNA cubes with tunable cellular uptake profiles Here, we demonstrate a new approach for the design and assembly of a dynamic DNA cube with an addressable cellular uptake profile. This cube can be selectively unzipped from a 3D to a flat two-dimensional structure in the presence of a specific nucleic acid sequence. Selective opening is demonstrated in vitro using a synthetic RNA marker unique to the LNCaP human prostate cancer cell line. A robust uptake in LNCaP cells, HeLa cells (human cervical cancer) and primary B-lymphocytes isolated from the blood of chronic lymphocytic leukemia (CLL) patients is observed using fluorescence-activated cell sorting (FACS), confocal microscopy and a new cluster analysis algorithm combined with image cross-correlation spectroscopy. The DNA cube was modified with hydrophobic and hydrophilic dendritic chains that were found to coat its exterior. The dynamic unzipping properties of these modified cubes were retained, and assessment of cellular uptake shows that the hydrophobic chains help with the rapid uptake of the constructs while the hydrophilic chains become advantageous for long term internalization. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Chemical Science Royal Society of Chemistry

Sequence-responsive unzipping DNA cubes with tunable cellular uptake profiles

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Publisher
Royal Society of Chemistry
Copyright
This journal is © the Partner Organisations 2014
ISSN
2041-6520
eISSN
2041-6539
DOI
10.1039/c4sc00646a
Publisher site
See Article on Publisher Site

Abstract

Here, we demonstrate a new approach for the design and assembly of a dynamic DNA cube with an addressable cellular uptake profile. This cube can be selectively unzipped from a 3D to a flat two-dimensional structure in the presence of a specific nucleic acid sequence. Selective opening is demonstrated in vitro using a synthetic RNA marker unique to the LNCaP human prostate cancer cell line. A robust uptake in LNCaP cells, HeLa cells (human cervical cancer) and primary B-lymphocytes isolated from the blood of chronic lymphocytic leukemia (CLL) patients is observed using fluorescence-activated cell sorting (FACS), confocal microscopy and a new cluster analysis algorithm combined with image cross-correlation spectroscopy. The DNA cube was modified with hydrophobic and hydrophilic dendritic chains that were found to coat its exterior. The dynamic unzipping properties of these modified cubes were retained, and assessment of cellular uptake shows that the hydrophobic chains help with the rapid uptake of the constructs while the hydrophilic chains become advantageous for long term internalization.

Journal

Chemical Science – Royal Society of Chemistry

Published: Mar 31, 2014

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