Delivery of Oligonucleotides and Analogues: The Oligonucleotide Conjugate‐Based Approach

Marlin, Fanny; Simon, Philippe; Saison‐Behmoaras, Tula; Giovannangéli, Carine

doi:10.1002/cbic.201000138

Cited by 22 publications

(20 citation statements)

References 73 publications

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“…This suggested that both cellular uptake and intracellular release from endosomes occurred efficiently. In contrast, unmodified [dN] 12 and S 2 [dN] 12 at much greater concentrations entered cells only 24 h post-treatment. Here, detection of fluorescence in lysosomes suggested that in these instances the mechanism of cell entry was pinocytosis [44].…”

mentioning

confidence: 68%

“…Examples of commonly conjugated units include hydrophobic residues, such as cholesterol and α-tocopherol, or cell-penetrating peptides that enhance membrane penetration [9][10][11][12][13], the polymer PEG, which decreases immunogenicity and enhances serum half-life [14] or intercalating groups to increase hybridization affinity [15]. An extensive literature already describes commonly used oligonucleotide conjugate chemistry, as well as the pharmacokinetic, pharmacodynamic and therapeutic properties of the product oligonucleotide conjugates [16][17][18][19][20][21][22].…”

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confidence: 99%

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Polyamine–Oligonucleotide Conjugates: A Promising Direction for Nucleic Acid Tools and Therapeutics

2015

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Chemical modification and/or the conjugation of small functional molecules to oligonucleotides have significantly improved their biological and biophysical properties, addressing issues such as poor cell penetration, stability to nucleases and low affinity for their targets. Here, the authors review the literature reporting on the biophysical, biochemical and biological properties of one particular class of modification - polyamine-oligonucleotide conjugates. Naturally derived and synthetic polyamines have been grafted onto a variety of oligonucleotide formats, including antisense oligonucleotides and siRNAs. In many cases this has had beneficial effects on their properties such as target hybridization, nuclease resistance, cellular uptake and activity. Polyamine-oligonucleotide conjugation, therefore, represents a promising direction for the further development of oligonucleotide-based therapeutics and tools.

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confidence: 68%

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confidence: 99%

Polyamine–Oligonucleotide Conjugates: A Promising Direction for Nucleic Acid Tools and Therapeutics

2015

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“…There is a growing literature on oligonucleotides conjugated to ligands designed to promote cellular uptake (Watts et al, 2008;Lonnberg, 2009;Marlin et al, 2010;Singh et al, 2010;Juliano et al, 2012b;Nguyen and Szoka, 2012). Conjugate groups can be incorporated into oligonucleotides by direct online synthesis on a DNA/RNA synthesizer or by post-synthetic conjugation to reactive groups incorporated during automated oligonucleotide synthesis.…”

Section: Oligonucleotide Conjugate Chemistrymentioning

confidence: 99%

Cellular Uptake and Intracellular Trafficking of Oligonucleotides: Implications for Oligonucleotide Pharmacology

Juliano

Xin

Carver

et al. 2014

Nucleic Acid Therapeutics

104

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One of the major constraints on the therapeutic use of oligonucleotides is inefficient delivery to their sites of action in the cytosol or nucleus. Recently it has become evident that the pathways of cellular uptake and intracellular trafficking of oligonucleotides can strongly influence their pharmacological actions. Here we provide background information on the basic processes of endocytosis and trafficking and then review recent literature on targeted delivery and subcellular trafficking of oligonucleotides in that context. A variety of approaches including molecular scale ligand-oligonucleotide conjugates, ligand-targeted nanocarriers, and the use of small molecules to enhance oligonucleotide effects are discussed.

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“…In addition to the CPP-oligonucleotide conjugates described above, there has been substantial work involving other covalent modifications of antisense and siRNA to enhance their biological properties, as summarized in several recent reviews 93-96 . Much of this has focused on conjugation with cholesterol or other lipophilic moieties to increase oligonucleotide lifetime in the circulation and to promote uptake via lipoprotein receptors in the liver and elsewhere 7,63,97 .…”

Section: Uptake and Trafficking Of Receptor Targeted Ligand-oligonmentioning

confidence: 99%

Cellular Uptake and Intracellular Trafficking of Antisense and siRNA Oligonucleotides

2011

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Significant progress is being made concerning the development of oligonucleotides as therapeutic agents. Studies with antisense, siRNA, and other forms of oligonucleotides have shown promise in cellular and animal models and in some clinical studies. Nonetheless our understanding of how oligonucleotides function in cells and tissues is really quite limited. One major issue concerns the modes of uptake and intracellular trafficking of oligonucleotides, whether as ‘free’ molecules, or linked to various delivery moieties such as nanoparticles or targeting ligands. In this review we examine the recent literature on oligonucleotide internalization and subcellular trafficking in the context of current insights into the basic machinery for endocytosis and intracellular vesicular traffic.

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Delivery of Oligonucleotides and Analogues: The Oligonucleotide Conjugate‐Based Approach

Cited by 22 publications

References 73 publications

Polyamine–Oligonucleotide Conjugates: A Promising Direction for Nucleic Acid Tools and Therapeutics

Polyamine–Oligonucleotide Conjugates: A Promising Direction for Nucleic Acid Tools and Therapeutics

Cellular Uptake and Intracellular Trafficking of Oligonucleotides: Implications for Oligonucleotide Pharmacology

Cellular Uptake and Intracellular Trafficking of Antisense and siRNA Oligonucleotides

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