Delivery of Oligonucleotides Using a Self-Degradable Lipid-Like Material

Tanaka, Hiroki; Takata, Nae; Sakurai, Yasuhisa; Yoshida, Tokuyuki; Inoué, Takao; Tamagawa, Shinya; Nakai, Yoshihisa; Tange, Kota; Yoshioka, Hiroki; Maeki, Masatoshi; Akita, Hidetaka

doi:10.3390/pharmaceutics13040544

Cited by 27 publications

(22 citation statements)

References 35 publications

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Section: Discussionmentioning

confidence: 99%

“…The limitation of the hemolysis assay was that the contribution of proteins cannot be evaluated. A hemolysis assay in the presence of serum would be a more accurate index for the expected efficiency of LNPs [42]. The LNP ssPalm with 0.75% of DMG-PEG2000 or 1.5% of DMG-PEG2000 was incubated with red blood cells at different pH from pH5.5 to pH 6.5.…”

Section: The Membrane Destabilizing Activity Was Enhanced By the Surface Modificationmentioning

confidence: 99%

“…The limitation of the hemolysis assay was that the contribution of proteins cannot be evaluated. A hemolysis assay in the presence of serum would be a more accurate index for the expected efficiency of LNPs [42]. Based on experiments involving pharmacological inhibitors of endocytosis, the findings revealed that the LNPssPalm particles were internalized into the Jurkat cells via clathrin-mediated endocytosis (CME).…”

Section: The Lnp Sspalm Was Taken Up By the Jurkat Cells Via Clathrin/dynamin-dependent Endocytosismentioning

confidence: 99%

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Improvement of mRNA Delivery Efficiency to a T Cell Line by Modulating PEG-Lipid Content and Phospholipid Components of Lipid Nanoparticles

et al. 2021

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(1) Background: T cells are important target cells, since they exert direct cytotoxic effects on infected/malignant cells, and affect the regulatory functions of other immune cells in a target antigen-specific manner. One of the current approaches for modifying the function of T cells is gene transfection by viral vectors. However, the insertion of the exogenous DNA molecules into the genome is attended by the risk of mutagenesis, especially when a transposon-based gene cassette is used. Based on this scenario, the transient expression of proteins by an in vitro-transcribed messenger RNA (IVT-mRNA) has become a subject of interest. The use of lipid nanoparticles (LNPs) for the transfection of IVT-mRNA is one of the more promising strategies for introducing exogenous genes. In this study, we report on the development of LNPs with transfection efficiencies that are comparable to that for electroporation in a T cell line (Jurkat cells). (2) Methods: Transfection efficiency was improved by optimizing the phospholipids and polyethylene glycol (PEG)-conjugated lipid components. (3) Results: Modification of the lipid composition resulted in the 221-fold increase in luciferase activity compared to a previously optimized formulation. Such a high transfection activity was due to the efficient uptake by clathrin/dynamin-dependent endocytosis and the relatively efficient escape into the cytoplasm at an early stage of endocytosis.

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Section: Discussionmentioning

confidence: 99%

Section: The Membrane Destabilizing Activity Was Enhanced By the Surface Modificationmentioning

confidence: 99%

“…The limitation of the hemolysis assay was that the contribution of proteins cannot be evaluated. A hemolysis assay in the presence of serum would be a more accurate index for the expected efficiency of LNPs [42]. Based on experiments involving pharmacological inhibitors of endocytosis, the findings revealed that the LNPssPalm particles were internalized into the Jurkat cells via clathrin-mediated endocytosis (CME).…”

Section: The Lnp Sspalm Was Taken Up By the Jurkat Cells Via Clathrin/dynamin-dependent Endocytosismentioning

confidence: 99%

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Improvement of mRNA Delivery Efficiency to a T Cell Line by Modulating PEG-Lipid Content and Phospholipid Components of Lipid Nanoparticles

et al. 2021

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“…However, the optimal composition of LNPs applicable to ASOs will vary, as will the key to successful delivery mechanisms [52,53]. Hiroki et al initially hypothesized that the optimal composition of ssPalmO-Phe/Chol for siRNA delivery could be applied to ASOs, but it was revealed that LNP ssPalmO-Phe containing ASOs are highly unstable and susceptible to aggregation [54]. With an improved lipid composition and lipid/ASO ratio, an LNP system that could efficiently transport ASOs was obtained.…”

Section: Lipid-based Delivery Systemsmentioning

confidence: 99%

Nonviral delivery systems for antisense oligonucleotide therapeutics

Huang

Hao

et al. 2022

Biomater Res

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Antisense oligonucleotides (ASOs) are an important tool for the treatment of many genetic disorders. However, similar to other gene drugs, vectors are often required to protect them from degradation and clearance, and to accomplish their transport in vivo. Compared with viral vectors, artificial nonviral nanoparticles have a variety of design, synthesis, and formulation possibilities that can be selected to accomplish protection and delivery for specific applications, and they have served critical therapeutic purposes in animal model research and clinical applications, allowing safe and efficient gene delivery processes into the target cells. We believe that as new ASO drugs develop, the exploration for corresponding nonviral vectors is inevitable. Intensive development of nonviral vectors with improved delivery strategies based on specific targets can continue to expand the value of ASO therapeutic approaches. Here, we provide an overview of current nonviral delivery strategies, including ASOs modifications, action mechanisms, and multi-carrier methods, which aim to address the irreplaceable role of nonviral vectors in the progressive development of ASOs delivery.

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“…Preclinical studies have used LNPs to deliver nucleic acids beyond siRNA and mRNA, such as antisense oligonucleotides (ASOs) [4] , microRNA [5] , and DNA [6] . Several clinical trials are currently assessing LNP delivery of a broad range of payloads, including the first in vivo CRISPR/Cas9 treatment delivered intravenously (i.v.)…”

Section: Introductionmentioning

confidence: 99%