Designing Chemically Modified Oligonucleotides for Targeted Gene Silencing

Abstract

Oligonucleotides (ONs), and their chemically modified mimics, are now routinely used in the laboratory as a means to control the expression of fundamentally interesting or therapeutically relevant genes. ONs are also under active investigation in the clinic, with many expressing cautious optimism that at least some ON-based therapies will succeed in the coming years. In this review, we will discuss several classes of ONs used for controlling gene expression, with an emphasis on antisense ONs (AONs), small interfering RNAs (siRNAs), and microRNA-targeting ONs (anti-miRNAs). This review provides a current and detailed account of ON chemical modification strategies for the optimization of biological activity and therapeutic application, while clarifying the biological pathways, chemical properties, benefits, and limitations of oligonucleotide analogs used in nucleic acids research.

Tandem DNAzymes for mRNA cleavage: Choice of enzyme, metal ions and the antisense effect

“…1 For example, antisense DNA relies on DNA oligomers to form a duplex with target mRNA and recruit RNase H to cleave the RNA strand. 2 With siRNA, the cellular RNA interference pathway is harnessed and the target mRNA is efficiently degraded.…”

Tandem Phosphorothioate Modifications for DNA Adsorption Strength and Polarity Control on Gold Nanoparticles

“…The best known example is probably for anti-sense DNA to be more resistant to nucleases. 25 It is also used for assembling metallic nanoparticles, [26][27][28] proteins, 29 or semiconductor quantum dots, 30,31 and for biosensor development. 32,33 PS modification is valuable for studying enzyme mechanism as well.…”

Synthesis and properties of DNA oligonucleotides with a zwitterionic backbone structure

“…Due to the reduced overall negative charge, we anticipate NAA-modified oligonucleotides to possibly display enhanced cellular uptake. Hence, the NAAlinkage might be a useful addition to the 'toolbox' of oligonucleotide modifications 2,3 for the design of therapeutic agents. It should also be noted that the amino group of the NAA-motif might be employed for the selective covalent derivatisation of oligonucleotides with fluorophores or other chemical entities.…”