A DNA-binding, albumin-targeting fusion protein promotes the cellular uptake and bioavailability of framework DNA nanostructure

Nanoscale ◽  
2021 ◽  
Author(s):  
Xue Li ◽  
Fan Xu ◽  
Donglei Yang ◽  
Pengfei Wang
Keyword(s):  
Dna Binding ◽  
Fusion Protein ◽  
Physicochemical Properties ◽  
Cellular Uptake ◽  
Dna Nanostructures ◽  
Surface Functionality ◽  
Dna Nanostructure

Framework DNA nanostructures exhibit unique characteristics such as precisely controllable physicochemical properties (i.e. size, shape, surface functionality) that have been used as carriers for the delivery of a variety of...

scholarly journals Ultrasound exposure enhances cellular uptake of nanoscale cargos

2021 ◽  
Author(s):  
Kahkashan Bansal ◽  
Anjali Rajwar ◽  
Himanshu Shekhar ◽  
Dhiraj Bhatia
Keyword(s):  
Drug Delivery ◽  
Cellular Uptake ◽  
Propidium Iodide ◽  
Dna Nanotechnology ◽  
Chemotherapeutic Agents ◽  
Dna Nanostructures ◽  
Ultrasound Exposure ◽  
Dna Nanostructure ◽  
Cellular Components ◽  
Further Development

DNA nanotechnology utilizes DNA as a structural molecule to design palette of nanostructures with different shapes and sizes. DNA nanocages have demonstrated significant potential for drug delivery. Therefore, enhancing the delivery of DNA nanocages into cells can improve their efficacy as drug delivery agents. Numerous studies have reported the effects of ultrasound for enhancing drug delivery across biological barriers. The mechanical bioeffects caused by cell-ultrasound interaction can cause sonoporation, leading to enhanced uptake of drugs, nanoparticles, and chemotherapeutic agents through membranes. Whether ultrasound exposure can enhance the delivery of DNA nanocages has not been explored, which is the focus of this study. Specifically, we investigated the effects of ultrasound on the cellular uptake of propidium Iodide, fluorescent dextrans, and DNA nanostructures). We provide evidence of modulation of pore formation in the cell membrane by ultrasound by studying the intracellular uptake of the impermeable dye, propidium iodide. Treatment of cells with low amplitudes of ultrasound enhanced the uptake of different sizes of dextrans and DNA based nanodevices. These findings could serve as the foundation for further development ultrasound-enabled DNA nanostructure delivery and for specific understanding of underlying biological mechanisms of interaction between ultrasound parameters and cellular components; the knowledge that can be further explored for potential biological and biomedical applications.

Peptide-nucleic acid nanostructures for transfection

2012 ◽  
Vol 3 (3) ◽  
pp. 283-293 ◽  
Author(s):  
Burkhard Bechinger
Keyword(s):  
Nucleic Acid ◽  
Physicochemical Properties ◽  
Cellular Uptake ◽  
Peptide Nucleic Acid ◽  
Endosomal Escape ◽  
Medical Applications ◽  
Specific Cell ◽  
Charge Composition ◽  
Cell Surfaces ◽  
Intracellular Targeting

AbstractTo use nucleic acids in biomedical research and medical applications, these highly hydrophilic macromolecules have to be transported through the organism, targeted to specific cell surfaces, and have to cross cellular barriers. To this end, nanosized transfection complexes have been designed and several of them have been successfully tested. Here, the different steps of the transfection process and the particular optimization protocols are reviewed, including the physicochemical properties of such vectors (size, charge, composition), protection in serum, cellular uptake, endosomal escape, and intracellular targeting. The transfection process has been subdivided into separate steps and here special emphasis is given to peptides that have been designed to optimize these steps individually. Finally, complex devices encompassing a multitude of beneficial functionalities for transfection have been developed.

Acquisition of NFKB1-selective DNA binding by substitution of four amino acid residues from NFKB1 into RelA

1993 ◽  
Vol 13 (7) ◽  
pp. 3850-3859
Author(s):  
T A Coleman ◽  
C Kunsch ◽  
M Maher ◽  
S M Ruben ◽  
C A Rosen
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Dna Binding ◽  
Fusion Protein ◽  
Binding Specificity ◽  
Single Amino Acid ◽  
Nf Kappa B ◽  
Dna Binding Specificity ◽  
Dna Motif ◽  
Single Amino Acid Change

The subunits of NF-kappa B, NFKB1 (formerly p50) and RelA (formerly p65), belong to a growing family of transcription factors that share extensive similarity to the c-rel proto-oncogene product. The homology extends over a highly conserved stretch of approximately 300 amino acids termed the Rel homology domain (RHD). This region has been shown to be involved in both multimerization (homo- and heterodimerization) and DNA binding. It is now generally accepted that homodimers of either subunit are capable of binding DNA that contains a kappa B site originally identified in the immunoglobulin enhancer. Recent studies have demonstrated that the individual subunits of the NF-kappa B transcription factor complex can be distinguished by their ability to bind distinct DNA sequence motifs. By using NFKB1 and RelA subunit fusion proteins, different regions within the RHD were found to confer DNA-binding and multimerization functions. A fusion protein that contains 34 N-terminal amino acids of NFKB1 and 264 amino acids of RelA displayed preferential binding to an NFKB1-selective DNA motif while dimerizing with the characteristics of RelA. Within the NFKB1 portion of this fusion protein, a single amino acid change of His to Arg altered the DNA-binding specificity to favor interaction with the RelA-selective DNA motif. Furthermore, substitution of four amino acids from NFKB1 into RelA was able to alter the DNA-binding specificity of the RelA protein to favor interaction with the NFKB1-selective site. Taken together, these findings demonstrate the presence of a distinct subdomain within the RHD involved in conferring the DNA-binding specificity of the Rel family of proteins.

scholarly journals Role of GCR2 in transcriptional activation of yeast glycolytic genes.

1992 ◽  
Vol 12 (9) ◽  
pp. 3834-3842 ◽  
Author(s):  
H Uemura ◽  
Y Jigami
Keyword(s):  
Dna Binding ◽  
Fusion Protein ◽  
Transcriptional Activation ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Gene Products ◽  
Lacz Expression ◽  
Genetic Method ◽  
Potential Interactions

The Saccharomyces cerevisiae GCR2 gene affects expression of most of the glycolytic genes. We report the nucleotide sequence of GCR2, which can potentially encode a 58,061-Da protein. There is a small cluster of asparagines near the center and a C-terminal region that would be highly charged but overall neutral. Fairly homologous regions were found between Gcr2 and Gcr1 proteins. To test potential interactions, the genetic method of S. Fields and O. Song (Nature [London] 340:245-246, 1989), which uses protein fusions of candidate gene products with, respectively, the N-terminal DNA-binding domain of Gal4 and the C-terminal activation domain II, assessing restoration of Gal4 function, was used. In a delta gal4 delta gal80 strain, double transformation by plasmids containing, respectively, a Gal4 (transcription-activating region)/Gcr1 fusion and a Gal4 (DNA-binding domain)/Gcr2 fusion activated lacZ expression from an integrated GAL1/lacZ fusion, indicating reconstitution of functional Gal4 through the interaction of Gcr1 and Gcr2 proteins. The Gal4 (transcription-activating region)/Gcr1 fusion protein alone complemented the defects of both gcr1 and gcr2 strains. Furthermore, a Rap1/Gcr2 fusion protein partially complemented the defects of gcr1 strains. These results suggest that Gcr2 has transcriptional activation activity and that the GCR1 and GCR2 gene products function together.

scholarly journals Bio-surface engineering with DNA scaffolds for theranostic applications

2018 ◽  
Vol 4 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Xiwei Wang ◽  
Wei Lai ◽  
Tiantian Man ◽  
Xiangmeng Qu ◽  
Li Li ◽  
...  
Keyword(s):  
Recent Progress ◽  
Surface Engineering ◽  
Dna Nanotechnology ◽  
Three Dimensions ◽  
High Yield ◽  
Biological Applications ◽  
Dna Nanostructures ◽  
Surface Functionality ◽  
Recognition Ability ◽  
Theranostic Applications

Abstract Biosensor design is important to bioanalysis yet challenged by the restricted target accessibility at the biomolecule-surface (bio-surface). The last two decades have witnessed the appearance of various “art-like” DNA nanostructures in one, two, or three dimensions, and DNA nanostructures have attracted tremendous attention for applications in diagnosis and therapy due to their unique properties (e.g., mechanical flexibility, programmable control over their shape and size, easy and high-yield preparation, precise spatial addressability and biocompatibility). DNA nanotechnology is capable of providing an effective approach to control the surface functionality, thereby increasing the molecular recognition ability at the biosurface. Herein, we present a critical review of recent progress in the development of DNA nanostructures in one, two and three dimensions and highlight their biological applications including diagnostics and therapeutics. We hope that this review provides a guideline for bio-surface engineering with DNA nanostructures.

An electrochemical aptasensor based on cocoon-like DNA nanostructure signal amplification for the detection of Escherichia coli O157:H7

The Analyst ◽  
2020 ◽  
Vol 145 (22) ◽  
pp. 7340-7348
Author(s):  
Huasong Bai ◽  
Shengjun Bu ◽  
Wensen Liu ◽  
Chengyu Wang ◽  
Zhongyi Li ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Signal Amplification ◽  
Selective Detection ◽  
Escherichia Coli O157 ◽  
Dna Nanostructures ◽  
Electrochemical Aptasensor ◽  
Dna Nanostructure ◽  
Highly Sensitive

We developed an electrochemical aptasensor based on cocoon-like DNA nanostructures as signal tags for highly sensitive and selective detection of Escherichia coli O157:H7.

scholarly journals DNA nanostructures coordinate gene silencing in mature plants

2019 ◽  
Vol 116 (15) ◽  
pp. 7543-7548 ◽  
Author(s):  
Huan Zhang ◽  
Gozde S. Demirer ◽  
Honglu Zhang ◽  
Tianzheng Ye ◽  
Natalie S. Goh ◽  
...  
Keyword(s):  
Cell Wall ◽  
Gene Silencing ◽  
Plant Cell ◽  
Mammalian Cells ◽  
Plant Cell Wall ◽  
Plant Cells ◽  
Design Parameters ◽  
Dna Nanostructures ◽  
Dna Nanostructure ◽  
The Impact

Delivery of biomolecules to plants relies onAgrobacteriuminfection or biolistic particle delivery, the former of which is amenable only to DNA delivery. The difficulty in delivering functional biomolecules such as RNA to plant cells is due to the plant cell wall, which is absent in mammalian cells and poses the dominant physical barrier to biomolecule delivery in plants. DNA nanostructure-mediated biomolecule delivery is an effective strategy to deliver cargoes across the lipid bilayer of mammalian cells; however, nanoparticle-mediated delivery without external mechanical aid remains unexplored for biomolecule delivery across the cell wall in plants. Herein, we report a systematic assessment of different DNA nanostructures for their ability to internalize into cells of mature plants, deliver siRNAs, and effectively silence a constitutively expressed gene inNicotiana benthamianaleaves. We show that nanostructure internalization into plant cells and corresponding gene silencing efficiency depends on the DNA nanostructure size, shape, compactness, stiffness, and location of the siRNA attachment locus on the nanostructure. We further confirm that the internalization efficiency of DNA nanostructures correlates with their respective gene silencing efficiencies but that the endogenous gene silencing pathway depends on the siRNA attachment locus. Our work establishes the feasibility of biomolecule delivery to plants with DNA nanostructures and both details the design parameters of importance for plant cell internalization and also assesses the impact of DNA nanostructure geometry for gene silencing mechanisms.

Cellular uptake of covalent and non-covalent DNA nanostructures with different sizes and geometries

Nanoscale ◽  
2019 ◽  
Vol 11 (22) ◽  
pp. 10808-10818 ◽  
Author(s):  
Sofia Raniolo ◽  
Stefano Croce ◽  
Rasmus P. Thomsen ◽  
Anders H. Okholm ◽  
Valeria Unida ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Dna Nanostructures ◽  
Intracellular Fate ◽  
In Cells

DNA nanostructures of different sizes and forms are internalized in cells through the LOX-1 receptor with different intracellular fate and lifetime.

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