Self-assembled DNA/RNA nanoparticles as a new generation of therapeutic nucleic acids: immunological compatibility and other translational considerations

AbstractTherapeutic nucleic acids (TNAs) are rapidly being embraced as effective interventions in a variety of genetic disorders, cancers, and viral/microbial infections, as well as for use in improving vaccine efficacy. Many traditional nucleotide-based formulations have been approved for clinical use, while various macromolecular nucleic acids are in different phases of preclinical and clinical development. Various nanotechnology carriers, including but not limited to liposomes, emulsions, dendrimers, and polyplexes, are considered for their improved delivery and reduced toxicity compared to traditional TNAs. Moreover, a new generation of TNAs has recently emerged and is represented by DNA/RNA nanoparticles formed by the self-assembly of DNA, RNA, or hybrid DNA-RNA oligonucleotides into 1D, 2D, and 3D structures of different shapes. In this mini-review, I will discuss immunocompatibility and other translational aspects in the development of this new class of promising nucleic acid therapeutics.

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Depsipeptide nucleic acids: prebiotic formation, oligomerization, and self-assembly of a new candidate proto-nucleic acid

10.1101/2020.09.01.278838 ◽

2020 ◽

Author(s):

David M. Fialho ◽

Suneesh C. Karunakaran ◽

Katherine W. Greeson ◽

Isaac Martínez ◽

Gary B. Schuster ◽

...

Keyword(s):

Nucleic Acid ◽

Nucleic Acids ◽

Self Assembly ◽

Rna World ◽

Chemical Components ◽

Early Earth ◽

New Class ◽

Self Assembling ◽

World Hypothesis ◽

Rna World Hypothesis

AbstractThe mechanism by which genetic polymers spontaneously formed on the early Earth is currently unknown. The RNA World hypothesis implies that RNA oligomers were produced prebiotically, but the demonstration of this process has proven challenging. Alternatively, RNA may be the product of evolution and some, or all, of its chemical components may have been preceded by functionally analogous moieties that were more readily accessible under plausible early-Earth conditions. We report a new class of nucleic acid analog, depsipeptide nucleic acid, which displays several properties that make it an attractive candidate for the first informational polymer to arise on the Earth. The monomers of depsipeptide nucleic acids can form under plausibly prebiotic conditions. These monomers oligomerize spontaneously when dried from aqueous solutions to form nucleobase-functionalized depsipeptides. Once formed, these depsipeptide nucleic acid oligomers are capable of complementary self-assembly, and are resistant to hydrolysis in the assembled state. These results suggest that the initial formation of primitive, self-assembling, informational polymers may have been relatively facile.

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Photoresponsive supramolecular coordination polyelectrolyte as smart anticounterfeiting inks

Nature Communications ◽

10.1038/s41467-021-21677-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Zhiqiang Li ◽

Xiao Liu ◽

Guannan Wang ◽

Bin Li ◽

Hongzhong Chen ◽

...

Keyword(s):

Self Assembly ◽

Ring Opening ◽

Resonance Energy Transfer ◽

Resonance Energy ◽

Ring Closure ◽

New Class ◽

Supramolecular Coordination ◽

Ligand Coordination ◽

Information Patterns ◽

New Generation

AbstractWhile photoluminescence printing is a widely applied anticounterfeiting technique, there are still challenges in developing new generation anticounterfeiting materials with high security. Here we report the construction of a photoresponsive supramolecular coordination polyelectrolyte (SCP) through hierarchical self-assembly of lanthanide ion, bis-ligand and diarylethene unit, driven by metal-ligand coordination and ionic interaction. Owing to the conformation-dependent photochromic fluorescence resonance energy transfer between the lanthanide donor and diarylethene acceptor, the ring-closure/ring-opening isomerization of the diarylethene unit leads to a photoreversible luminescence on/off switch in the SCP. The SCP is then utilized as security ink to print various patterns, through which photoreversible multiple information patterns with visible/invisible transformations are realized by simply alternating the irradiation with UV and visible light. This work demonstrates the possibility of developing a new class of smart anticounterfeiting materials, which could be operated in a noninvasive manner with a higher level of security.

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Viscoelastic behavior of chemically fueled supramolecular hydrogels under load and influence of reaction side products

Communications Materials ◽

10.1038/s43246-021-00202-6 ◽

2021 ◽

Vol 2 (1) ◽

Author(s):

Martin Kretschmer ◽

Benjamin Winkeljann ◽

Brigitte A. K. Kriebisch ◽

Job Boekhoven ◽

Oliver Lieleg

Keyword(s):

Self Assembly ◽

Linear Response ◽

Viscoelastic Behavior ◽

Shear Load ◽

Mechanical Forces ◽

Waste Products ◽

New Class ◽

Synthetic Materials ◽

New Generation

AbstractAbout ten years ago, chemically fueled systems have emerged as a new class of synthetic materials with tunable properties. Yet, applications of these materials are still scarce. In part, this is due to an incomplete characterization of the viscoelastic properties of those materials, which has – so far – mostly been limited to assessing their linear response under shear load. Here, we fill some of these gaps by comparing the viscoelastic behavior of two different, carbodiimide fueled Fmoc-peptide systems. We find that both, the linear and non-linear response of the hydrogels formed by those Fmoc-peptides depends on the amount of fuel driving the self-assembly process – but hardly on the direction of force application. In addition, we identify the concentration of accumulated waste products as a novel, so far neglected parameter that crucially affects the behavior of such chemically fueled hydrogels. With the mechanistic insights gained here, it should be possible to engineer a new generation of dynamic hydrogels with finely tunable material properties that can be tailored precisely for such applications, where they are challenged by mechanical forces.

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A Bottom-Up Approach to Solution-Processed, Atomically Precise Graphitic Cylinders on Surfaces

10.26434/chemrxiv.7158959 ◽

2018 ◽

Author(s):

Erik Leonhardt ◽

Jeff M. Van Raden ◽

David Miller ◽

Lev N. Zakharov ◽

Benjamin Aleman ◽

...

Keyword(s):

Self Assembly ◽

Carbon Nanostructures ◽

Carbon Nanomaterials ◽

Circle Packing ◽

Pyrolytic Graphite ◽

Building Blocks ◽

Bottom Up ◽

Casting Technique ◽

New Class ◽

Solution Casting Technique

Extended carbon nanostructures, such as carbon nanotubes (CNTs), exhibit remarkable properties but are difficult to synthesize uniformly. Herein, we present a new class of carbon nanomaterials constructed via the bottom-up self-assembly of cylindrical, atomically-precise small molecules. Guided by supramolecular design principles and circle packing theory, we have designed and synthesized a fluorinated nanohoop that, in the solid-state, self-assembles into nanotube-like arrays with channel diameters of precisely 1.63 nm. A mild solution-casting technique is then used to construct vertical “forests” of these arrays on a highly-ordered pyrolytic graphite (HOPG) surface through epitaxial growth. Furthermore, we show that a basic property of nanohoops, fluorescence, is readily transferred to the bulk phase, implying that the properties of these materials can be directly altered via precise functionalization of their nanohoop building blocks. The strategy presented is expected to have broader applications in the development of new graphitic nanomaterials with π-rich cavities reminiscent of CNTs.

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A theorized new class of polyhedral hydrocarbons of molecular formula CnHn and their bottom-up scaffold expansions into hyperstructures

Scientific Reports ◽

10.1038/s41598-021-84562-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Camila M. B. Machado ◽

Nathalia B. D. Lima ◽

Sóstenes L. S. Lins ◽

Alfredo M. Simas

Keyword(s):

General Formula ◽

Chemical Structure ◽

Molecular Formula ◽

Fusion Reactions ◽

3D Scaffold ◽

3D Scaffolds ◽

Bottom Up ◽

New Class ◽

Euler’S Theorem ◽

2D And 3D

AbstractWe address the use of Euler's theorem and topological algorithms to design 18 polyhedral hydrocarbons of general formula CnHn that exist up to 28 vertexes containing four- and six-membered rings only; compounds we call “nuggets”. Subsequently, we evaluated their energies to verify the likelihood of their chemical existence. Among these compounds, 13 are novel systems, of which 3 exhibit chirality. Further, the ability of all nuggets to perform fusion reactions either through their square faces, or through their hexagonal faces was evaluated. Indeed, they are potentially able to form bottom-up derived molecular hyperstructures with great potential for several applications. By considering these fusion abilities, the growth of the nuggets into 1D, 2D, and 3D-scaffolds was studied. The results indicate that nugget24a (C24H24) is predicted to be capable of carrying out fusion reactions. From nugget24a, we then designed 1D, 2D, and 3D-scaffolds that are predicted to be formed by favorable fusion reactions. Finally, a 3D-scaffold generated from nugget24a exhibited potential to be employed as a voxel with a chemical structure remarkably similar to that of MOF ZIF-8. And, such a voxel, could in principle be employed to generate any 3D sculpture with nugget24a as its level of finest granularity.

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Silencing Antibiotic Resistance with Antisense Oligonucleotides

Biomedicines ◽

10.3390/biomedicines9040416 ◽

2021 ◽

Vol 9 (4) ◽

pp. 416

Author(s):

Saumya Jani ◽

Maria Soledad Ramirez ◽

Marcelo E. Tolmasky

Keyword(s):

Antibiotic Resistance ◽

Nucleic Acids ◽

Antisense Oligonucleotides ◽

Bacterial Infections ◽

Genetic Disorders ◽

Antibiotic Resistance Genes ◽

Short Review ◽

Rnase H ◽

Biological Processes ◽

Locked Nucleic Acids

Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for the treatment of a very diverse group of diseases including viral and bacterial infections, genetic disorders, and cancer. To date, drugs approved for utilization in clinics or in clinical trials target diseases other than bacterial infections. Although several groups and companies are working on different strategies, the application of antisense technologies to prokaryotes still lags with respect to those that target other human diseases. In those cases where the focus is on bacterial pathogens, a subset of the research is dedicated to produce antisense compounds that silence or reduce expression of antibiotic resistance genes. Therefore, these compounds will be adjuvants administered with the antibiotic to which they reduce resistance levels. A varied group of oligonucleotide analogs like phosphorothioate or phosphorodiamidate morpholino residues, as well as peptide nucleic acids, locked nucleic acids and bridge nucleic acids, the latter two in gapmer configuration, have been utilized to reduce resistance levels. The major mechanisms of inhibition include eliciting cleavage of the target mRNA by the host’s RNase H or RNase P, and steric hindrance. The different approaches targeting resistance to β-lactams include carbapenems, aminoglycosides, chloramphenicol, macrolides, and fluoroquinolones. The purpose of this short review is to summarize the attempts to develop antisense compounds that inhibit expression of resistance to antibiotics.

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Molecular self-assembly of copolymer from renewable phenols: new class of antimicrobial ointment base

Journal of Biomaterials Science Polymer Edition ◽

10.1080/09205063.2018.1531483 ◽

2018 ◽

Vol 29 (18) ◽

pp. 2187-2200 ◽

Cited By ~ 1

Author(s):

Denial Mahata ◽

Santi M. Mandal

Keyword(s):

Self Assembly ◽

New Class ◽

Ointment Base

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Encapsulation and Ultrasound-Triggered Release of G-Quadruplex DNA in Multilayer Hydrogel Microcapsules

Polymers ◽

10.3390/polym10121342 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1342 ◽

Cited By ~ 4

Author(s):

Aaron Alford ◽

Brenna Tucker ◽

Veronika Kozlovskaya ◽

Jun Chen ◽

Nirzari Gupta ◽

...

Keyword(s):

Nucleic Acids ◽

Defense Mechanisms ◽

The Body ◽

Stimuli Responsive ◽

Triggered Release ◽

Quadruplex Dna ◽

Nucleic Acid Therapeutics ◽

Wide Range ◽

G Quadruplex ◽

Hydrogel Capsules

Nucleic acid therapeutics have the potential to be the most effective disease treatment strategy due to their intrinsic precision and selectivity for coding highly specific biological processes. However, freely administered nucleic acids of any type are quickly destroyed or rendered inert by a host of defense mechanisms in the body. In this work, we address the challenge of using nucleic acids as drugs by preparing stimuli responsive poly(methacrylic acid)/poly(N-vinylpyrrolidone) (PMAA/PVPON)n multilayer hydrogel capsules loaded with ~7 kDa G-quadruplex DNA. The capsules are shown to release their DNA cargo on demand in response to both enzymatic and ultrasound (US)-triggered degradation. The unique structure adopted by the G-quadruplex is essential to its biological function and we show that the controlled release from the microcapsules preserves the basket conformation of the oligonucleotide used in our studies. We also show that the (PMAA/PVPON) multilayer hydrogel capsules can encapsulate and release ~450 kDa double stranded DNA. The encapsulation and release approaches for both oligonucleotides in multilayer hydrogel microcapsules developed here can be applied to create methodologies for new therapeutic strategies involving the controlled delivery of sensitive biomolecules. Our study provides a promising methodology for the design of effective carriers for DNA vaccines and medicines for a wide range of immunotherapies, cancer therapy and/or tissue regeneration therapies in the future.

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