Lipid–oligonucleotide conjugates for bioapplications

Li, Xiaowei; Feng, Keqin; Li, Long; Lu, Yang; Pan, Xiaoshu; Yazd, Hoda Safari; Cui, Cheng; Li, Juan; Moroz, Leonid L.; Sun, Yujia; Wang, Bang; Huang, T. C.; Tan, Weihong

doi:10.1093/nsr/nwaa161

Cited by 56 publications

(54 citation statements)

References 116 publications

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“…Given the knowledge of genes and their role accessibility, incurable genetic disorders are made possible through this novel approach. Its application is not merely limited to drug discovery but also pertinent for investigations of the mechanism and stereochemistry of biochemical reactions, mapping of nucleic acid-protein interactions, and diagnostic applications [2]. ON therapy is well aligned to play a noteworthy role in speeding up drug discovery against traditionally undruggable targets.…”

Section: Background Of Oligonucleotidementioning

confidence: 99%

Delivery of Oligonucleotides: Efficiency with Lipid Conjugation and Clinical Outcome

et al. 2022

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Oligonucleotides have shifted drug discovery into a new paradigm due to their ability to silence the genes and inhibit protein translation. Importantly, they can drug the un-druggable targets from the conventional small-molecule perspective. Unfortunately, poor cellular permeability and susceptibility to nuclease degradation remain as major hurdles for the development of oligonucleotide therapeutic agents. Studies of safe and effective delivery technique with lipid bioconjugates gains attention to resolve these issues. Our review article summarizes the physicochemical effect of well-studied hydrophobic moieties to enhance the cellular entry of oligonucleotides. The structural impacts of fatty acids, cholesterol, tocopherol, and squalene on cellular internalization and membrane penetration in vitro and in vivo were discussed first. The crucial assays for delivery evaluation within this section were analyzed sequentially. Next, we provided a few successful examples of lipid-conjugated oligonucleotides advanced into clinical studies for treating patients with different medical backgrounds. Finally, we pinpointed current limitations and outlooks in this research field along with opportunities to explore new modifications and efficacy studies.

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Section: Background Of Oligonucleotidementioning

confidence: 99%

Delivery of Oligonucleotides: Efficiency with Lipid Conjugation and Clinical Outcome

et al. 2022

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“…[ 24 ] The challenge to this method is that the lipid moieties have to withstand reaction stress without degradation during SPS. [ 25 ] For the second method, the lipids and the nucleic acids need to have reactive groups for interaction. Some general methods have been developed to form different linkers for nucleic acids and lipids in buffered solution, including thioether, [ 26 ] phosphoester, and triazole linkers.…”

Section: Construction Strategies For Nucleic Acid‐modified Liposomesmentioning

confidence: 99%

Nucleic Acid‐Modified Liposome: Construction Methods and Biological Applications

Liang

Zhu

et al. 2021

Adv Materials Inter

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Liposomes with excellent biocompatibility have been widely used in nutraceutical and biomedical fields for delivery of bioactive molecules. Functional nucleic acids including aptamers that have good target recognizing ability and molecular assembly properties can be used to modify liposomes to expand their applications. This review comprehensively summarizes and comparatively discusses the construction strategies including covalent methods, noncovalent methods, and protein‐mediated methods for fabricating nucleic acid‐modified liposomes. Their applications in stability enhancement, biosensing, drug delivery, and synthesis of biomimetic structures are then reviewed. From above, it is concluded that the nucleic acid‐modified liposome, as a newly developed advanced material, has a good potential to be applied for biosensor or pharmaceutical purposes.

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“…One of the ways to overcome the limitations of poor cellular uptake is through the conjugation (a covalent attachment) of an oligonucleotide or its analogue to a moiety that promotes cellular penetration. A number of such carriers from small molecules to macromolecules and supramolecular assemblies have been proposed, such as cholesterol [ 22 , 23 , 24 ] and other lipids [ 25 , 26 , 27 ]; polymers [ 28 ], in particular, polyethyleneimine [ 29 ]; dendrimers [ 30 ]; inorganic nanoparticles [ 31 ]; DNA nanostructures [ 32 , 33 ]; and others [ 34 ]. However, despite the tremendous progress in non-viral nucleic acid delivery over the past 25 years [ 35 ], there is still no consistent solution for conjugation with such moieties that would be applicable to most cell types and a wide range of biological targets that can significantly improve the in vivo efficacy of the prospective oligonucleotide therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Chemistry of Peptide-Oligonucleotide Conjugates: A Review

2021

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Peptide-oligonucleotide conjugates (POCs) represent one of the increasingly successful albeit costly approaches to increasing the cellular uptake, tissue delivery, bioavailability, and, thus, overall efficiency of therapeutic nucleic acids, such as, antisense oligonucleotides and small interfering RNAs. This review puts the subject of chemical synthesis of POCs into the wider context of therapeutic oligonucleotides and the problem of nucleic acid drug delivery, cell-penetrating peptide structural types, the mechanisms of their intracellular transport, and the ways of application, which include the formation of non-covalent complexes with oligonucleotides (peptide additives) or covalent conjugation. The main strategies for the synthesis of POCs are viewed in detail, which are conceptually divided into (a) the stepwise solid-phase synthesis approach and (b) post-synthetic conjugation either in solution or on the solid phase, especially by means of various click chemistries. The relative advantages and disadvantages of both strategies are discussed and compared.

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Lipid–oligonucleotide conjugates for bioapplications

Cited by 56 publications

References 116 publications

Delivery of Oligonucleotides: Efficiency with Lipid Conjugation and Clinical Outcome

Delivery of Oligonucleotides: Efficiency with Lipid Conjugation and Clinical Outcome

Nucleic Acid‐Modified Liposome: Construction Methods and Biological Applications

Chemistry of Peptide-Oligonucleotide Conjugates: A Review

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