Biomotors, viral assembly, and RNA nanobiotechnology: Current achievements and future directions

Rolband, Lewis; Beasock, Damian; Wang, Yang; Shu, Yeqiang; Dinman, Jonathan D.; Schlick, Tamar; Zhou, Yaoqi; Kieft, Jeffrey; Chen, Shi‐Jie; Bussi, Giovanni; Oukhaled, Abdelghani; Gao, Xingfa; Šulc, Petr; Binzel, Daniel W.; Bhullar, Abhjeet S.; Liang, Chenxi; Guo, Peixuan; Afonin, Kirill A.

doi:10.1016/j.csbj.2022.11.007

Cited by 15 publications

(7 citation statements)

References 213 publications

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“…We believe that the proposed approach for reversible changes in molecularity and shape of complexes will be a valuable tool for the rational design of therapeutic nucleic acids highly targeted with a programmable response of the immune system of organisms [ 11 , 12 , 55 ]. The results obtained in this paper open up new perspectives and abilities for RNA nanotechnology and RNA nanomachines.…”

Section: Discussionmentioning

confidence: 99%

Diversity of Self-Assembled RNA Complexes: From Nanoarchitecture to Nanomachines

Kanarskaya,

Pyshnyi,

Lomzov

2023

Molecules

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New tool development for various nucleic acid applications is an essential task in RNA nanotechnology. Here, we determined the ability of self-limited complex formation by a pair of oligoribonucleotides carrying two pairwise complementary blocks connected by a linker of different lengths in each chain. The complexes were analyzed using UV melting, gel shift assay analysis, and molecular dynamics (MD) simulations. We have demonstrated the spontaneous formation of various self-limited and concatemer complexes. The linear concatemer complex is formed by a pair of oligomers without a linker in at least one of them. Longer linkers resulted in the formation of circular complexes. The self-limited complexes formation was confirmed using the toehold strand displacement. The MD simulations indicate the reliability of the complexes’ structure and demonstrate their dynamics, which increase with the rise of complex size. The linearization of 2D circular complexes into 1D structures and a reverse cyclization process were demonstrated using a toehold-mediated approach. The approach proposed here for the construction and directed modification of the molecularity and shape of complexes will be a valuable tool in RNA nanotechnology, especially for the rational design of therapeutic nucleic acids with high target specificity and the programmable response of the immune system of organisms.

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Section: Discussionmentioning

confidence: 99%

Diversity of Self-Assembled RNA Complexes: From Nanoarchitecture to Nanomachines

Kanarskaya,

Pyshnyi,

Lomzov

2023

Molecules

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“…RNA can serve either as a therapeutic that is delivered or as a substrate targeted by drugs. In recent years, RNA has gained focus in pharmaceutic and vaccine field, most notably through the FDA approval of RNA-based therapeutics − and authorization of mRNA COVID-19 vaccines. − These approvals confirm the safety and stability of RNA in clinical applications. − RNA therapeutics have now emerged as a prominent field and is becoming the third milestone in pharmaceutical drug development. − …”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Evaluation of the Pathology and Safety Aspects of Three- and Four-Way Junction RNA Nanoparticles

Jin,

Liao,

Cheng

et al. 2024

Mol. Pharmaceutics

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RNA therapeutics has advanced into the third milestone in pharmaceutical drug development, following chemical and protein therapeutics. RNA itself can serve as therapeutics, carriers, regulators, or substrates in drug development. Due to RNA's motile, dynamic, and deformable properties, RNA nanoparticles have demonstrated spontaneous targeting and accumulation in cancer vasculature and fast excretion through the kidney glomerulus to urine to prevent possible interactions with healthy organs. Furthermore, the negatively charged phosphate backbone of RNA results in general repulsion from negatively charged lipid cell membranes for further avoidance of vital organs. Thus, RNA nanoparticles can spontaneously enrich tumor vasculature and efficiently enter tumor cells via specific targeting, while those not entering the tumor tissue will clear from the body quickly. These favorable parameters have led to the expectation that RNA has low or little toxicity. RNA nanoparticles have been well characterized for their anticancer efficacy; however, little detail on RNA nanoparticle pathology and safety is known. Here, we report the in vitro and in vivo assessment of the pathology and safety aspects of different RNA nanoparticles including RNA three-way junction (3WJ) harboring 2′-F modified pyrimidine, folic acid, and Survivin siRNA, as well as the RNA four-way junction (4WJ) harboring 2′-F modified pyrimidine and 24 copies of SN38. Both animal models and patient serum were investigated. In vitro studies include hemolysis, platelet aggregation, complement activation, plasma coagulation, and interferon induction. In vivo studies include hematoxylin and eosin (H&E) staining, hematological and biochemical analysis as the serum profiling, and animal organ weight study. No significant toxicity, side effect, or immune responses were detected during the extensive safety evaluations of RNA nanoparticles. These results further complement previous cancer inhibition studies and demonstrate RNA nanoparticles as an effective and safe drug delivery vehicle for future clinical translations.

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“…Nucleic acid (NA) nanotechnology utilizes the complementary nature of NA to construct complex assemblies with discrete secondary structures through canonical Watson–Crick interactions. − This approach has led to the creation of numerous NA-based nanoscaffolds of 1D, 2D, and 3D shapes with different connectivities and the ability to act as targeted delivery vehicles or carriers for other functionalities. , Over the past two decades, significant contributions have been made toward the development of NA-based nanoscaffolds through molecular self-assembly, pioneered by the work of Nadrian Seeman in the DNA nanotechnology field as well as Neocles Leontis, Eric Westhof, and Peixuan Guo in the RNA nanotechnology and therapeutic RNA nanotechnology fields. This has led to the construction of diverse 1D, 2D, and 3D NA nanoscaffolds, including cubes, polygons, tetrahedra, bipyramids, dodecahedra, etc., which have been demonstrated to be effective in targeted delivery. − For instance, prior research led by Seeman and collaborators utilized this concept to create innovative DNA-based nanomaterials through DNA self-assembly.…”

Section: Introductionmentioning

confidence: 99%

Design and Characterization of Compact, Programmable, Multistranded Nonimmunostimulatory Nucleic Acid Nanoparticles Suitable for Biomedical Applications

Brumett,

Danai,

Coffman

et al. 2024

Biochemistry

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We report a thorough investigation of the role of single-stranded thymidine (ssT) linkers in the stability and flexibility of minimal, multistranded DNA nanostructures. We systematically explore the impact of varying the number of ssTs in three-way junction motifs (3WJs) on their formation and properties. Through various UV melting experiments and molecular dynamics simulations, we demonstrate that while the number of ssTs minimally affects thermodynamic stability, the increasing ssT regions significantly enhance the structural flexibility of 3WJs. Utilizing this knowledge, we design triangular DNA nanoparticles with varying ssTs, all showing exceptional assembly efficiency except for the 0T triangle. All triangles demonstrate enhanced stability in blood serum and are nonimmunostimulatory and nontoxic in mammalian cell lines. The 4T 3WJ is chosen as the building block for constructing other polygons due to its enhanced flexibility and favorable physicochemical characteristics, making it a versatile choice for creating cost-effective, stable, and functional DNA nanostructures that can be stored in the dehydrated forms while retaining their structures. Our study provides valuable insights into the design and application of nucleic acid nanostructures, emphasizing the importance of understanding stability and flexibility in the realm of nucleic acid nanotechnology. Our findings suggest the intricate connection between these ssTs and the structural adaptability of DNA 3WJs, paving the way for more precise design and engineering of nucleic acid nanosystems suitable for broad biomedical applications.

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Biomotors, viral assembly, and RNA nanobiotechnology: Current achievements and future directions

Cited by 15 publications

References 213 publications

Diversity of Self-Assembled RNA Complexes: From Nanoarchitecture to Nanomachines

Diversity of Self-Assembled RNA Complexes: From Nanoarchitecture to Nanomachines

In Vitro and In Vivo Evaluation of the Pathology and Safety Aspects of Three- and Four-Way Junction RNA Nanoparticles

Design and Characterization of Compact, Programmable, Multistranded Nonimmunostimulatory Nucleic Acid Nanoparticles Suitable for Biomedical Applications

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