The delivery of therapeutic oligonucleotides

By R. Juliano. Nucleic Acids Research, 2016

743 citations recorded by the source corpus.

The oligonucleotide therapeutics field has seen remarkable progress over the last few years with the approval of the first antisense drug and with promising developments in late stage clinical trials using siRNA or splice switching oligonucleotides. However, effective delivery of oligonucleotides to their intracellular sites of action remains a major issue. This review will describe the biological basis of oligonucleotide delivery including the nature of various tissue barriers and the mechanisms of cellular uptake and intracellular trafficking of oligonucleotides. It will then examine a variety of current approaches for enhancing the delivery of oligonucleotides. This includes molecular scale targeted ligand-oligonucleotide conjugates, lipid- and polymer-based nanoparticles, antibody conjugates and small molecules that improve oligonucleotide delivery. The merits and liabilities of these approaches will be discussed in the context of the underlying basic biology.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bf4c45e76215f25371a8e4c2bd51b706ae563c32

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In Molecular Biology

1. Aaron D Springer
2. M. Manoharan
3. Martin Egli
4. S. Dowdy

Citations in the corpus

• Chemistry, structure and function of approved oligonucleotide therapeutics (2023, background): “Therefore, understanding the intracellular trafficking machinery and breaching the endosomal barrier critically affect the design and clinical success of oligonucleotide therapeutics (356).”
• GalNAc-siRNA Conjugates: Leading the Way for Delivery of RNAi Therapeutics (2018, background): “Early approaches focused on lipid nanoparticles (LNPs) and synthetic nanoparticles to address the siRNA delivery problem that were predicated on several decades worth of nanoparticle delivery approaches developed for large DNA gene therapy vectors [2,4].”