Solid-Phase Synthesis of Oligonucleotide Conjugates Useful for Delivery and Targeting of Potential Nucleic Acid Therapeutics

Abstract

Olignucleotide-based drugs show promise as a novel form of chemotherapy. Among the hurdles that have to be overcome on the way of applicable nucleic acid therapeutics, inefficient cellular uptake and subsequent release from endosomes to cytoplasm appear to be the most severe ones. Covalent conjugation of oligonucleotides to molecules that expectedly facilitate the internalization, targets the conjugate to a specific cell-type or improves the parmacokinetics offers a possible way to combat against these shortcomings. Since workable chemistry is a prerequisite for biological studies, development of efficient and reproducible methods for preparation of various types of oligonucleotide conjugates has become a subject of considerable importance. The present review summarizes the advances made in the solid-supported synthesis of oligonucleotide conjugates aimed at facilitating the delivery and targeting of nucleic acid drugs.

Aminosilane functionalizations of mesoporous oxidized silicon for oligonucleotide synthesis and detection

“…Since we have demonstrated the stability of aminosilanized PSi on exposure to carbonate/dry methanol solutions, the use of the so-called 'ultramild' phosphoramidites can be also exploited in future experiments: this result will open the prospect of PSi solid phase ON synthesis without any restriction on the ON composition sequence, giving more general significance to the proposed methodology. In addition to biosensors and microarrays, solid-supported synthesis of ON conjugates will facilitate delivery and targeting of nucleic acid drugs, thus unlocking a very innovative and promising route to new kinds of chemotherapy and other exciting medical challenges [23].…”

Synthesis and in vitro inhibition properties of siRNA conjugates carrying glucose and galactose with different presentations

“…Among the different approaches described to prepare carbohydrate oligonucleotide conjugates [19,20] we selected the protocol based on the coupling of a sugar phophoramidite to oligonucleotides on a solid support. This approach has been previously used in our group to introduce several sugars in DNA [14,15].…”

Oligonucleotide Tagging for Copper-Free Click Conjugation

“…Generally, such applications require the introduction of a suitable handle in an oligonucleotide to enable selective conjugation to a functionality of interest [6][7][8]. For example, attachment of a cell-penetrating ligand is the most commonly applied strategy to tackle the low internalization rate of ONs into target cells [2], currently the main bottleneck in oligonucleotide-based therapeutics (antisense, siRNA).…”