Determinants of Ligand-Functionalized DNA Nanostructure–Cell Interactions

Cremers, Glenn A.O.; Rosier, Bas J.H.M.; Meijs, Ab; Tito, Nicholas B.; Duijnhoven, Sander M.J. van; Eenennaam, Hans van; Albertazzi, Lorenzo; Greef, Tom F. A. de

doi:10.1021/jacs.1c02298

Cited by 47 publications

(41 citation statements)

References 63 publications

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“…[ 137 , 145 ]. Besides answering questions regarding nanotechnology, NA constructs can also answer fundamental biological questions, such as receptors organization [ 162 ], cell interactions [ 163 ] or intracellular processes [ 164 , 165 ]. For example, it was recently shown that compaction and cholesterol tagging of structures could increase specificity towards certain blood cells [ 166 ], or that mechanical properties could promote tumour accumulation [ 167 ].…”

Section: Emerging Rna-based Technologiesmentioning

confidence: 99%

Innovative developments and emerging technologies in RNA therapeutics

et al. 2022

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RNA-based therapeutics are emerging as a powerful platform for the treatment of multiple diseases. Currently, the two main categories of nucleic acid therapeutics, antisense oligonucleotides and small interfering RNAs (siRNAs), achieve their therapeutic effect through either gene silencing, splicing modulation or microRNA binding, giving rise to versatile options to target pathogenic gene expression patterns. Moreover, ongoing research seeks to expand the scope of RNA-based drugs to include more complex nucleic acid templates, such as messenger RNA, as exemplified by the first approved mRNA-based vaccine in 2020. The increasing number of approved sequences and ongoing clinical trials has attracted considerable interest in the chemical development of oligonucleotides and nucleic acids as drugs, especially since the FDA approval of the first siRNA drug in 2018. As a result, a variety of innovative approaches is emerging, highlighting the potential of RNA as one of the most prominent therapeutic tools in the drug design and development pipeline. This review seeks to provide a comprehensive summary of current efforts in academia and industry aimed at fully realizing the potential of RNA-based therapeutics. Towards this, we introduce established and emerging RNA-based technologies, with a focus on their potential as biosensors and therapeutics. We then describe their mechanisms of action and their application in different disease contexts, along with the strengths and limitations of each strategy. Since the nucleic acid toolbox is rapidly expanding, we also introduce RNA minimal architectures, RNA/protein cleavers and viral RNA as promising modalities for new therapeutics and discuss future directions for the field.

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Section: Emerging Rna-based Technologiesmentioning

confidence: 99%

Innovative developments and emerging technologies in RNA therapeutics

et al. 2022

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“…As various antibodies represent distinct dimensions, their biological activity involving binding affinity also gets influenced [ 31 ]. Cremers et al [ 32 ] have utilized antibody surface grafted DNA nanostructures to demonstrate that although the inherent affinity of targeting antibody remains unaltered, the number of antibody–receptor interactions remains lower than soluble antibodies governed by nanoconstruct’s size and orientation. Based on these observations, the authors concluded that larger DNA nanostructures may cause steric hindrance and are the primary cause of reduced receptor binding potential.…”

Section: Design and Development Of Multivalent Targeted Nanosystemsmentioning

confidence: 99%

Critical parameters for design and development of multivalent nanoconstructs: recent trends

Bakshi

Haider

Tiwari

et al. 2022

Drug Deliv. and Transl. Res.

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Graphical abstract A century ago, the groundbreaking concept of the magic bullet was given by Paul Ehrlich. Since then, this concept has been extensively explored in various forms to date. The concept of multivalency is among such advancements of the magic bullet concept. Biologically, the concept of multivalency plays a critical role in significantly huge numbers of biochemical interactions. This concept is the sole reason behind the higher affinity of biological molecules like viruses to more selectively target the host cell surface receptors. Multivalent nanoconstructs are a promising approach for drug delivery by the active targeting principle. Designing and developing effective and target-specific multivalent drug delivery nanoconstructs, on the other hand, remain a challenge. The underlying reason for this is a lack of understanding of the crucial interactions between ligands and cell surface receptors, as well as the design of nanoconstructs. This review highlights the need for a better theoretical understanding of the multivalent effect of what happens to the receptor–ligand complex after it has been established. Furthermore, the critical parameters for designing and developing robust multivalent systems have been emphasized. We have also discussed current advances in the design and development of multivalent nanoconstructs for drug delivery. We believe that a thorough knowledge of theoretical concepts and experimental methodologies may transform a brilliant idea into clinical translation.

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“…295 However, compared with the extensive research on the interaction between DNA ligand patterns and cells, research on the effect of the ligand pattern on the DNA structure on virus recognition is still rare at present. 296,297 Therefore, further research is required in this field.…”

Section: Interaction Between Dendrimers and Virusesmentioning

confidence: 99%