Dynamic constitutional frameworks (DCFs) as nanovectors for cellular delivery of DNA

2015 ◽  
Vol 13 (34) ◽  
pp. 9005-9011 ◽  
Author(s):  
Ioana-Andreea Turin-Moleavin ◽  
Florica Doroftei ◽  
Adina Coroaba ◽  
Dragos Peptanariu ◽  
Mariana Pinteala ◽  
...  
Keyword(s):  
Cellular Delivery ◽  
Double Stranded Dna

We introduce Dynamic Constitutional Frameworks (DCFs), macromolecular structures that efficiently bind and transfect double stranded DNA.

Discrimination of monomer from multimer DNA disk-shaped toruses by freezeetch TEM

1984 ◽  
Vol 42 ◽  
pp. 210-211
Author(s):  
George C. Ruben ◽  
Kenneth A. Marx
Keyword(s):  
Biochemical Data ◽  
Dna Structures ◽  
Ice Surface ◽  
Double Stranded Dna ◽  
Data Support ◽  
Dna Organization ◽  
Trivalent Cations

In vitro collapse of DNA by trivalent cations like spermidine produces torus (donut) shaped DNA structures thought to have a DNA organization similar to certain double stranded DNA bacteriophage and viruses. This has prompted our studies of these structures using freeze-etch low Pt-C metal (9Å) replica TEM. With a variety of DNAs the TEM and biochemical data support a circumferential DNA winding model for hydrated DNA torus organization. Since toruses are almost invariably oriented nearly horizontal to the ice surface one of the most accessible parameters of a torus population is annulus (ring) thickness. We have tabulated this parameter for populations of both nicked, circular (Fig. 1: n=63) and linear (n=40: data not shown) ϕX-174 DNA toruses. In both cases, as can be noted in Fig. 1, there appears to be a compact grouping of toruses possessing smaller dimensions separated from a dispersed population possessing considerably larger dimensions.

Synchrony of Digestion of SV40 DNA by Exonuclease III Determined by EM

1975 ◽  
Vol 33 ◽  
pp. 674-675
Author(s):  
Ray Wu ◽  
G. Ruben ◽  
B. Siegel ◽  
P. Spielman ◽  
E. Jay
Keyword(s):  
Dark Field ◽  
Uranyl Acetate ◽  
Enzyme Digestion ◽  
Dna Molecules ◽  
Exonuclease Iii ◽  
Aluminum Films ◽  
Double Stranded Dna ◽  
Before And After ◽  
Exo Iii ◽  
Sv40 Dna

A method for determining long nucleotide sequences of double-stranded DNA is being developed. It involves (a) the synchronous digestion of the DNA from the 3' ends with EL coli exonuclease III (Exo III) followed by (b) resynthesis with labeled nucleotides and DNA polymerase. A crucial factor in the success of this method is the degree to which the enzyme digestion proceeds synchronously under proper conditions of incubation (step a). Dark field EM is used to obtain accurate measurements on the lengths and distribution of the DNA molecules before and after digestion with Exo III, while gel electrophoresis is used in parallel to obtain a mean length for these molecules. It is the measurements on a large enough sample of individual molecules by EM that provides the information on how synchronously the digestion proceeds. For length measurements, the DNA molecules were picked up on 20-30 Å thick carbon-aluminum films, using the aqueous Kleinschmidt technique and stained with 7.5 x 10-5M uranyl acetate in 90% ethanol for 3 minutes.

Torus Circumference and Thickness Parameters From a Linear DNA Size Series Suggest How Toruses Self-Assemble

1985 ◽  
Vol 43 ◽  
pp. 522-523
Author(s):  
George C. Ruben ◽  
Kenneth A. Marx
Keyword(s):  
Tertiary Structure ◽  
Dna Complexes ◽  
Tertiary Structures ◽  
Self Assembling ◽  
Double Stranded Dna ◽  
Calf Thymus ◽  
Dna Organization ◽  
Condensed Dna ◽  
Dna Size

Certain double stranded DNA bacteriophage and viruses are thought to have their DNA organized into large torus shaped structures. Morphologically, these poorly understood biological DNA tertiary structures resemble spermidine-condensed DNA complexes formed in vitro in the total absence of other macromolecules normally synthesized by the pathogens for the purpose of their own DNA packaging. Therefore, we have studied the tertiary structure of these self-assembling torus shaped spermidine- DNA complexes in a series of reports. Using freeze-etch, low Pt-C metal (10-15Å) replicas, we have visualized the microscopic DNA organization of both calf Thymus( CT) and linear 0X-174 RFII DNA toruses. In these structures DNA is circumferentially wound, continuously, around the torus into a semi-crystalline, hexagonal packed array of parallel DNA helix sections.

Dissecting the Therapeutic Relevance of Gene Therapy in NeuroAIDS: An Evolving Epidemic

2020 ◽  
Vol 20 (3) ◽  
pp. 174-183
Author(s):  
Bushra Nabi ◽  
Saleha Rehman ◽  
Faheem Hyder Pottoo ◽  
Sanjula Baboota ◽  
Javed Ali
Keyword(s):  
Viral Entry ◽  
Due Process ◽  
Intrinsic Property ◽  
Antiretroviral Drugs ◽  
Viral Reservoir ◽  
Primary Concern ◽  
Cellular Delivery ◽  
Formidable Challenge ◽  
Neurological Conditions ◽  
The Brain

: NeuroAIDS, a disease incorporating both infectious and neurodegenerative pathways, is still a formidable challenge for the researchers to deal with. The primary concern for the treatment of neuroAIDS still remains the inaccessibility of the viral reservoir, making it indispensable for novel techniques to be continuously innovated. Since the brain serves as a reservoir for viral replication, it is pragmatic and a prerequisite to overcome the related barriers in order to improve the drug delivery to the brain. The current treatment ideology is based on the combinatorial approach of a mocktail of antiretroviral drugs. However, complete eradication of the disease could not be achieved. Thereby the arena of gene-based cellular delivery is trending and has created a niche for itself in the present scenario. To establish the supremacy of gene delivery, it is advisable to have a better understanding of the molecular mechanism involved in the due process. The mechanism associated with the activity of the anti-HIV gene lies in their intrinsic property to impart resistance to the HIV infection by targeting the viral entry channels. This review principally emphasizes on different types of gene therapies explored so far for the management of AIDS and its associated neurological conditions. Therefore it could rightly be said that we are at the crossroad where the need of the hour is to develop novel strategies for curbing AIDS and its associated neurological conditions.

Analysis of unintegrated avian RNA tumor virus double-stranded DNA intermediates.

1978 ◽  
Vol 28 (3) ◽  
pp. 810-818 ◽  
Author(s):  
T W Hsu ◽  
J L Sabran ◽  
G E Mark ◽  
R V Guntaka ◽  
J M Taylor
Keyword(s):  
Double Stranded Dna ◽  
Tumor Virus

scholarly journals Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Federica Palombarini ◽  
Silvia Masciarelli ◽  
Alessio Incocciati ◽  
Francesca Liccardo ◽  
Elisa Di Fabio ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Targeted Delivery ◽  
Myeloid Leukemia ◽  
Electrostatic Interactions ◽  
Archaeoglobus Fulgidus ◽  
Leukemia Cells ◽  
Cellular Delivery ◽  
Self Assembling ◽  
Wide Range ◽  
Hybrid Nanoparticle

Abstract Background In recent years, the use of ferritins as nano-vehicles for drug delivery is taking center stage. Compared to other similar nanocarriers, Archaeoglobus fulgidus ferritin is particularly interesting due to its unique ability to assemble-disassemble under very mild conditions. Recently this ferritin was engineered to get a chimeric protein targeted to human CD71 receptor, typically overexpressed in cancer cells. Results Archaeoglobus fulgidus chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together with a small nucleic acid. The positively charged dendrimer can indeed establish electrostatic interactions with the chimeric ferritin internal surface, allowing the formation of a protein-dendrimer binary system. The 4 large triangular openings on the ferritin shell represent a gate for negatively charged small RNAs, which access the internal cavity attracted by the dense positive charge of the dendrimer. This ternary protein-dendrimer-RNA system is efficiently uptaken by acute myeloid leukemia cells, typically difficult to transfect. As a proof of concept, we used a microRNA whose cellular delivery and induced phenotypic effects can be easily detected. In this article we have demonstrated that this hybrid nanoparticle successfully delivers a pre-miRNA to leukemia cells. Once delivered, the nucleic acid is released into the cytosol and processed to mature miRNA, thus eliciting phenotypic effects and morphological changes similar to the initial stages of granulocyte differentiation. Conclusion The results here presented pave the way for the design of a new family of protein-based transfecting agents that can specifically target a wide range of diseased cells. Graphic abstract

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