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Title: In Situ Loading and Delivery of Short Single- and Double-Stranded DNA by Supramolecular Organic Frameworks

Abstract

Short DNA represents an important class of biomacromolecules that are widely applied in gene therapy, editing, and modulation. However, the development of simple and reliable methods for their intracellular delivery remains a challenge. Herein, we describe that seven water-soluble, homogeneous supramolecular organic frameworks (SOFs) with a well-defined pore size and high stability in water that can accomplish in situ inclusion of single-stranded (ss) and double-stranded (ds) DNA (21, 23, and 58 nt) and effective intracellular delivery (including two noncancerous and six cancerous cell lines). Fluorescence quenching experiments for single and double end-labeled ss- and ds-DNA support that the DNA sequences can be completely enveloped by the SOFs. Confocal laser scanning microscopy and flow cytometry reveal that five of the SOFs exhibit excellent delivery efficiencies that, in most of the studied cases, outperform the commercial standard Lipo2000, even at low SOF–nucleic acid ratios. In addition to high delivery efficiencies, the water-soluble, self-assembled SOF carriers have a variety of advantages, including convenient preparation, high stability, and in situ DNA inclusion, which are all critical for practical applications in nucleic acid delivery.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [2];  [1];  [1];  [3];  [1];  [1]
  1. Fudan Univ., Shanghai (China)
  2. Univ. of Macau, Taipa, Macao (China)
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Natural Science Foundation of China (NNSFC)
OSTI Identifier:
1599800
Grant/Contract Number:  
AC02-05CH11231; 21432004; 21529201
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
CCS Chemistry
Additional Journal Information:
Journal Volume: 1; Journal Issue: 2; Journal ID: ISSN 2096-5745
Publisher:
Chinese Chemical Society Publishing
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; nucleic acid delivery; electrostatic interaction; self-assembly; porous polymer; homogenous carrier

Citation Formats

Yang, Bo, Zhang, Xiao-Dan, Li, Jian, Tian, Jia, Wu, Yi-Peng, Yu, Fa-Xing, Wang, Ruibing, Wang, Hui, Zhang, Dan-Wei, Liu, Yi, Zhou, Liu, and Li, Zhan-Ting. In Situ Loading and Delivery of Short Single- and Double-Stranded DNA by Supramolecular Organic Frameworks. United States: N. p., 2019. Web. doi:10.31635/ccschem.019.20180011.
Yang, Bo, Zhang, Xiao-Dan, Li, Jian, Tian, Jia, Wu, Yi-Peng, Yu, Fa-Xing, Wang, Ruibing, Wang, Hui, Zhang, Dan-Wei, Liu, Yi, Zhou, Liu, & Li, Zhan-Ting. In Situ Loading and Delivery of Short Single- and Double-Stranded DNA by Supramolecular Organic Frameworks. United States. doi:10.31635/ccschem.019.20180011.
Yang, Bo, Zhang, Xiao-Dan, Li, Jian, Tian, Jia, Wu, Yi-Peng, Yu, Fa-Xing, Wang, Ruibing, Wang, Hui, Zhang, Dan-Wei, Liu, Yi, Zhou, Liu, and Li, Zhan-Ting. Tue . "In Situ Loading and Delivery of Short Single- and Double-Stranded DNA by Supramolecular Organic Frameworks". United States. doi:10.31635/ccschem.019.20180011. https://www.osti.gov/servlets/purl/1599800.
@article{osti_1599800,
title = {In Situ Loading and Delivery of Short Single- and Double-Stranded DNA by Supramolecular Organic Frameworks},
author = {Yang, Bo and Zhang, Xiao-Dan and Li, Jian and Tian, Jia and Wu, Yi-Peng and Yu, Fa-Xing and Wang, Ruibing and Wang, Hui and Zhang, Dan-Wei and Liu, Yi and Zhou, Liu and Li, Zhan-Ting},
abstractNote = {Short DNA represents an important class of biomacromolecules that are widely applied in gene therapy, editing, and modulation. However, the development of simple and reliable methods for their intracellular delivery remains a challenge. Herein, we describe that seven water-soluble, homogeneous supramolecular organic frameworks (SOFs) with a well-defined pore size and high stability in water that can accomplish in situ inclusion of single-stranded (ss) and double-stranded (ds) DNA (21, 23, and 58 nt) and effective intracellular delivery (including two noncancerous and six cancerous cell lines). Fluorescence quenching experiments for single and double end-labeled ss- and ds-DNA support that the DNA sequences can be completely enveloped by the SOFs. Confocal laser scanning microscopy and flow cytometry reveal that five of the SOFs exhibit excellent delivery efficiencies that, in most of the studied cases, outperform the commercial standard Lipo2000, even at low SOF–nucleic acid ratios. In addition to high delivery efficiencies, the water-soluble, self-assembled SOF carriers have a variety of advantages, including convenient preparation, high stability, and in situ DNA inclusion, which are all critical for practical applications in nucleic acid delivery.},
doi = {10.31635/ccschem.019.20180011},
journal = {CCS Chemistry},
issn = {2096-5745},
number = 2,
volume = 1,
place = {United States},
year = {2019},
month = {6}
}

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