Protecting microRNAs from RNase degradation with steric DNA nanostructures

Qian, Hang; Tay, Chor Yong; Setyawati, Magdiel Inggrid; Chia, Sing Ling; Lee, Di Sheng; Leong, David Tai

doi:10.1039/c6sc01829g

Cited by 68 publications

(50 citation statements)

References 44 publications

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“…DNA strands can be modified with cellular recognition signals, such as folate, transferrin, or aptamers, which permit the assembly of functionalized DNA-based nanostructures (DNS) useful for selective targeting into cells through receptor-mediated mechanism [3][4][5]. Due to their intrinsic biocompatible, nontoxic, and stable properties, DNS have been extensively investigated for various biomedical applications, such as drug delivery, cellular biosensing, and in vivo imaging [4][5][6][7][8], and, more recently, in gene silencing and RNA anticancer therapy [9,10]. Different shape-changing structural modules can be integrated in the DNS, allowing input-induced conformational changes.…”

Section: Introductionmentioning

confidence: 99%

In Silico and In Cell Analysis of Openable DNA Nanocages for miRNA Silencing

Raniolo

Iacovelli

Unida

et al. 2019

IJMS

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A computational and experimental integrated approach was applied in order to study the effect of engineering four DNA hairpins into an octahedral truncated DNA nanocage, to obtain a nanostructure able to recognize and bind specific oligonucleotide sequences. Modeling and classical molecular dynamics simulations show that the new H4-DNA nanocage maintains a stable conformation with the closed hairpins and, when bound to complementary oligonucleotides produces an opened conformation that is even more stable due to the larger hydrogen bond number between the hairpins and the oligonucleotides. The internal volume of the open conformation is much larger than the closed one, switching from 370 to 650 nm3, and the predicted larger conformational change is experimentally detectable by gel electrophoresis. H4-DNA nanocages display high stability in serum, can efficiently enter the cells where they are stable and maintain the ability to bind, and sequester an intracellular-specific oligonucleotide. Moreover, H4-DNA nanocages, modified in order to recognize the oncogenic miR21, are able to seize miRNA molecules inside cells in a selective manner.

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Section: Introductionmentioning

confidence: 99%

In Silico and In Cell Analysis of Openable DNA Nanocages for miRNA Silencing

Raniolo

Iacovelli

Unida

et al. 2019

IJMS

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“…So these DNA motifs have been used to trigger host immune response as these are recognized by TLR-9 located on endosomes of host membrane of immune system which activates the innate immune pathway of host immune system. Similarly, siRNA and miRNA delivery have also been carried out using DNA nanostructures for gene silencing applications (Lee et al, 2012;Fakhoury et al, 2013;Bujold et al, 2016;Roh et al, 2016;Qian et al, 2017;Nahar et al, 2018). Various types of DNA nanostructures, that have been used as delivery vehicles, are listed in Table 4 (Hu et al, 2018;Madhanagopal et al, 2018).…”

Section: Dna Nanotechnology-based Drug Deliverymentioning

confidence: 99%

Nanoscale Self-Assembly for Therapeutic Delivery

Yadav

Sharma

Kumar

2020

Front. Bioeng. Biotechnol.

203

149

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Self-assembly is the process of association of individual units of a material into highly arranged/ordered structures/patterns. It imparts unique properties to both inorganic and organic structures, so generated, via non-covalent interactions. Currently, selfassembled nanomaterials are finding a wide variety of applications in the area of nanotechnology, imaging techniques, biosensors, biomedical sciences, etc., due to its simplicity, spontaneity, scalability, versatility, and inexpensiveness. Self-assembly of amphiphiles into nanostructures (micelles, vesicles, and hydrogels) happens due to various physical interactions. Recent advancements in the area of drug delivery have opened up newer avenues to develop novel drug delivery systems (DDSs) and selfassembled nanostructures have shown their tremendous potential to be used as facile and efficient materials for this purpose. The main objective of the projected review is to provide readers a concise and straightforward knowledge of basic concepts of supramolecular self-assembly process and how these highly functionalized and efficient nanomaterials can be useful in biomedical applications. Approaches for the self-assembly have been discussed for the fabrication of nanostructures. Advantages and limitations of these systems along with the parameters that are to be taken into consideration while designing a therapeutic delivery vehicle have also been outlined. In this review, various macro-and small-molecule-based systems have been elaborated. Besides, a section on DNA nanostructures as intelligent materials for future applications is also included.

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“…Nevertheless, their biomedical application is still in its infancy. Due to the nature of DNA, this new class of material is sensibly considered a potential smart material platform as drug delivery vehicles, sensors and other functional units . Thus far, self‐assembled DNA nanostructures have been successfully explored as drug delivery vehicles for small molecule drugs, siRNA, proteins and other guest molecules in vitro or in vivo.…”

Section: Figurementioning

confidence: 99%

“…Numerous studies have revealed that DNA nanostructures showed certain stabilities compared with single‐stranded or duplex nucleic acid under physiological conditions . It was believed that the stability of DNA nanostructures is attributed to the steric effect and highly associated with the structural design. In the present study, we also evaluated the thermal and physiological stabilities of DNA nanoprism with PAGE.…”

Section: Figurementioning

confidence: 99%

Targeted Delivery of Rab26 siRNA with Precisely Tailored DNA Prism for Lung Cancer Therapy

Liu

Wang

et al. 2019

ChemBioChem

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Programmable DNA nanostructures are a new class of biocompatible, nontoxic nanomaterials. Nevertheless, their application in the field of biomedical research is still in its infancy, especially as drug delivery vehicles for gene therapy. In this study, a GTPase Rab26 was investigated as a new potential therapeutic target using a precisely tailored DNA nanoprism for targeted lung cancer therapy. Specifically, a DNA nanoprism platform with tunable targeting and siRNA loading capability is designed and synthesized. The as‐prepared DNA prisms were decorated with two functional units: a Rab26 siRNA as the drug and MUC‐1 aptamers as a targeting moiety for non‐small cell lung cancer. The number and position of both siRNA and MUC‐1 aptamers can be readily tuned by switching two short, single‐stranded DNA. Native polyacrylamide gel electrophoresis (PAGE) and dynamic light scattering technique (DLS) demonstrate that all nanoprisms with different functionalities are self‐assembled with high yield. It is also found that the cellular uptake of DNA prisms is proportional to the aptamer number on each nanoprism, and the as‐prepared DNA nanoprism show excellent anti‐cancer activities and targeting capability. This study suggests that by careful design, self‐assembled DNA nanostructures are highly promising, customizable, multifunctional nanoplatforms for potential biomedical applications, such as personalized precision therapy.

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Protecting microRNAs from RNase degradation with steric DNA nanostructures

Abstract: A DNA nanostructure bearing a “Shuriken” shape is designed to deliver, protect and activate microRNA-145 functionality in human colorectal cancer cells. This novel DNA nanostructure enabled therapeutic platform greatly suppresses cancer cell proliferation and tumor growth.

Cited by 68 publications

References 44 publications

In Silico and In Cell Analysis of Openable DNA Nanocages for miRNA Silencing

In Silico and In Cell Analysis of Openable DNA Nanocages for miRNA Silencing

Nanoscale Self-Assembly for Therapeutic Delivery

Targeted Delivery of Rab26 siRNA with Precisely Tailored DNA Prism for Lung Cancer Therapy

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