Journal article
Development of a novel DNA oligonucleotide targeting low-density lipoprotein receptor
Molecular Therapy - Nucleic Acids, Vol.19, pp.190-198
2019
Abstract
Low-density lipoprotein receptor (LDL-R) is a cell surface receptor protein expressed in a variety of solid cancers including lung, colon, breast, brain and liver, therefore opens up opportunities to deliver lysosome sensitive anti-cancer agents, especially synthetic nucleic acid-based therapeutic mole- cules. In this study, we focused on developing novel nucleic acid molecules specific to LDL-R. For this purpose, we performed in vitro selection procedure via SELEX methodologies using mammalian cell- expressed human recombinant LDL-R protein as a target. After ten rounds of selections, we identified a novel DNA oligonucleotide aptamer, RNV-L7, that can bind specifically to LDL-R protein with high affinity and specificity (Kd = 19.6 nM). Furthermore, flow cytometry and fluorescence imaging assays demonstrated efficient binding to LDL-R over-expressed human cancer cells including Huh-7 liver can- cer cells and MDA-MB-231 breast cancer cells with a binding affinity of ∼200 nM. Furthermore, we evaluated the functional potential of the developed LDL-R aptamer RNV-L7 by conjugating with a pre- viously reported miR-21 targeting DNAzyme for inhibiting miR-21 expression. The results showed that the miR-21 DNAzyme-RNV-L7 aptamer chimera efficiently reduced the expression of miR-21 in Huh- 7 liver cancer cells. As currently there are no reports on LDL-R aptamer development, we believe that RNV-L7 could be beneficial towards the development of targeted cancer therapeutics.
Details
- Title
- Development of a novel DNA oligonucleotide targeting low-density lipoprotein receptor
- Authors/Creators
- T. Wang (Author/Creator) - Murdoch UniversityK. Rahimizadeh (Author/Creator) - Murdoch UniversityR.N. Veedu (Author/Creator) - Murdoch University
- Publication Details
- Molecular Therapy - Nucleic Acids, Vol.19, pp.190-198
- Publisher
- Elsevier
- Identifiers
- 991005540542007891
- Copyright
- © 2019 The Author(s).
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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- Domestic collaboration
- Citation topics
- 2 Chemistry
- 2.145 Biosensors
- 2.145.243 Nanobiosensors
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- Medicine, Research & Experimental
- ESI research areas
- Biology & Biochemistry