Aptamers as Modular Components of Therapeutic Nucleic Acid Nanotechnology

Abstract

Nucleic acids play a central role in all domains of life, either as genetic blueprints or as regulators of various biochemical pathways. The chemical makeup of ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), generally represented by a sequence of four monomers, also provides precise instructions for folding and higher-order assembly of these biopolymers that, in turn, dictate biological functions. The sequence-based specific 3D structures of nucleic acids led to the development of the directed evolution of oligonucleotides, SELEX (systematic evolution of ligands by exponential enrichment), against a chosen target molecule. Among the variety of functions, selected oligonucleotides named aptamers also allow targeting of cell-specific receptors with antibody-like precision and can deliver functional RNAs without a transfection agent. The advancements in the field of customizable nucleic acid nanoparticles (NANPs) opened avenues for the design of nanoassemblies utilizing aptamers for triggering or blocking cell signaling pathways or using aptamer-receptor combinations to activate therapeutic functionalities. A recent selection of fluorescent aptamers enables real-time tracking of NANP formation and interactions. The aptamers are anticipated to contribute to the future development of technologies, enabling an efficient assembly of functional NANPs in mammalian cells or in vivo. These research topics are *

Induction of Cytokines by Nucleic Acid Nanoparticles (NANPs) Depends on the Type of Delivery Carrier

“…The field of RNA and DNA nanotechnology is rapidly growing. In the past decade, researchers have established various approaches to synthesize RNA and DNA nanoassemblies of different sizes, shapes, and compositions and generated proof-of-concept data intended for the use of these materials in biology and medicine [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. A growing library of nucleic acid nanoparticles (NANPs), the design of which takes advantage of natural RNA (and DNA) motifs and canonical Watson–Crick base pairings, have been demonstrated to assemble into precise nanoscaffolds exemplified by hexagonal rings [ 12 ], various polygons [ 13 ], and fibrous structures [ 14 ], to name a few [ 15 ].…”

Modified internucleoside linkages for nuclease-resistant oligonucleotides

“…Since the discovery of their structures and their roles as carriers of genetic information, the biological understanding of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) has evolved to versatile bioscaffolds with applications in many areas related to biology. Important discoveries include their therapeutic use as antisense (AS) agents, 1,2 small interfering RNAs (siRNAs), 3,4 CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) associated protein 9 (CRISPR-Cas9), 5,6 antigen (triplex-forming oligonucleotide) 7,8 molecules, aptamers, [9][10][11] and primers for gene amplification through polymerase chain reaction (PCR) 12,13 or gene sequencing, [14][15][16][17] and many other applications related to biotechnology such as the elaboration of DNA microarrays, 18,19 site-specific mutagenesis, 20 Southern blotting and Northern blotting. 21 In the specific field of DNA-based in vivo gene regulation therapies, nuclease resistance is a prerequisite for oligodeoxynucleotides (ODN) to allow them to reach their target and have observable therapeutic effects in the presence of a plethora of nucleases in serum and cells.…”

Polyamine‐Functionalized 2′‐Amino‐LNA in Oligonucleotides: Facile Synthesis of New Monomers and High‐Affinity Binding towards ssDNA and dsDNA

“…[3,14,15] Different strategies have been proposed to improve the intracellular delivery of ONs. [16][17][18][19][20][21][22][23] Amongt hem, bioconjugationof polyamines and cationic cell-penetrating peptides to ONs are notable examples that affect the overall charge state of the resulting ONs. [15,[24][25][26] The issue of nuclease stabilityc an at least in part be tackledb yi ntroducing chemicalm odifications or replacing the naturalr ibose-phosphate backbone with artificial analogues.…”