Abstract
Nucleic acids are programmable and biocompatible polymers that have beneficial uses in nanotechnology with broad applications in biosensing and therapeutics. In some cases, however, the development of the latter has been impeded by the unknown immunostimulatory properties of nucleic acid-based materials, as well as a lack of functional dynamicity due to stagnant structural design. Recent research advancements have explored these obstacles in tandem via the assembly of three-dimensional, planar, and fibrous cognate nucleic acid-based nanoparticles, called NANPs, for the conditional activation of embedded and otherwise quiescent functions. Furthermore, a library of the most representative NANPs was extensively analyzed in human peripheral blood mononuclear cells (PBMCs), and the links between the programmable architectural and physicochemical parameters of NANPs and their immunomodulatory properties have been established. This overview will cover the recent development of design principles that allow for fine-tuning of both the physicochemical and immunostimulatory properties of dynamic NANPs and discuss the potential impacts of these novel strategies.
Highlights
Nanotechnology has been integrated into many aspects of modern life [1] by providing a means of additional control over the unique physicochemical properties of functional moieties—including size, surface charge, and hydrophobicity, as well as their precise incorporation—and making them useful for biomedical applications
The ability to fine-tune these properties subsequently allows for the improved efficacy of therapeutic treatments and has implications for the future of personalized medicine [2,3,4,5]. Nucleic acids, including both DNA and RNA, represent a branch of biopolymers which offer a biocompatible and programmable therapeutic approach. Beyond their traditionally known roles as passive carriers of genetic information, DNA and RNA have emerged as building materials for versatile biological drugs, called therapeutic nucleic acids (TNAs), which can take advantage of cellular pathways for the sensing, targeting, and silencing of a broad spectrum of various diseases, including asthma, cystic fibrosis, viral infections, and cancers [6,7]
TNAs are a diverse class of biomacromolecules that include antisense oligonucleotides, triplex-forming oligodeoxyribonucleotides, immunostimulatory oligos, catalytic oligos, inhibitory DNAs, interfering RNAs, and aptamers, which differ by composition, secondary structure, and mechanism of action [8]
Summary
Nanotechnology has been integrated into many aspects of modern life [1] by providing a means of additional control over the unique physicochemical properties of functional moieties—including size, surface charge, and hydrophobicity, as well as their precise incorporation—and making them useful for biomedical applications. The ability to fine-tune these properties subsequently allows for the improved efficacy of therapeutic treatments and has implications for the future of personalized medicine [2,3,4,5] Nucleic acids, including both DNA and RNA, represent a branch of biopolymers which offer a biocompatible and programmable therapeutic approach. Though TNAs in general and NANP-based nano-TNAs in particular are strong candidates in nanotherapeutics, their transition into a clinical setting has been hindered by a lack of general knowledge about their immunostimulatory properties [55], while their statically designed structures have posed limits to the conditional activation or deactivation of preprogrammed biological functions To overcome these obstacles, recent efforts, as described in this review, have been focused on a new platform of design principles for assembling dynamic nucleic acid assemblies with a controlled and fine-tunable immune response (Figure 1)
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