Design of lipid nanoparticles for in vitro and in vivo delivery of plasmid DNA

Kulkarni, Jayesh A.; Myhre, J. Layne; Chen, Sam; Tam, Yun K.; Danescu, Adrian; Richman, Joy M.; Cullis, Pieter R.

doi:10.1016/j.nano.2016.12.014

Cited by 157 publications

(153 citation statements)

References 42 publications

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“…Recent work by Kulkarni et al. demonstrated that the helper lipid can have a significant effect on plasmid DNA delivery and/or gene expression in five human cancer cell lines . Therefore, we also investigated if the presence of helper lipids such as 1,2‐dioleoyl‐ sn ‐glycero‐3‐phosphocholine (DOPC), 1,2‐distearoyl‐ sn ‐glycero‐3‐phosphocholine (DSPC), or 1‐stearoyl‐2‐oleoyl‐ sn ‐glycero‐3‐phosphocholine (SOPC) in LNP formulations could enhance transgene expression or posttransfection viability in mast cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…identified the novel cationic lipid DLinKC2‐DMA, which was highly effective at delivering siRNA to cells in vitro and in vivo . During the preparation of this manuscript, the Cullis group was first to demonstrate that LNPs containing DLinKC2‐DMA were highly effective at delivering plasmid DNA into a variety of human cancer cell lines . Therefore, we were interested to assess the ability of DLinKC2‐DMA to deliver plasmid DNA into HMC lines.…”

Section: Resultsmentioning

confidence: 99%

“…20 Although the generation and use of siRNA-LNPs has been well documented, 21 only a few examples of DNA-containing LNPs (≤100 nm) generated using spontaneous mixing or microfluidics have been shown to deliver plasmid DNA into mammalian cells. [22][23][24] None of these studies to date have investigated if LNPs are suitable vehicles for nucleic acid delivery into mast cells.…”

Section: Mast Cells Respond To a Variety Of Soluble Mediators Throughmentioning

confidence: 99%

“…16 During the preparation of this manuscript, the Cullis group was first to demonstrate that LNPs containing DLinKC2-DMA were highly effective at delivering plasmid DNA into a variety of human cancer cell lines. 24 Therefore, we were interested to assess the ability of DLinKC2-DMA to deliver plasmid DNA into HMC lines. We observed that DLinKC2-DMA-containing LNPs were highly efficient at encapsulating plasmid DNA at various cationic lipid mol% and formed nearly 100 nm sized particles ( Supplementary Table S2), similar to our data obtained using 50% DODAP and 50% DODMA containing LNPs.…”

Section: Cells (Comparementioning

confidence: 99%

“…Moreover, formulating LNPs using microfluidic mixing enhances the reproducibility and scalability of LNPs further facilitating their adoption as human therapeutics . Although the generation and use of siRNA‐LNPs has been well documented, only a few examples of DNA‐containing LNPs (≤100 nm) generated using spontaneous mixing or microfluidics have been shown to deliver plasmid DNA into mammalian cells . None of these studies to date have investigated if LNPs are suitable vehicles for nucleic acid delivery into mast cells.…”

Section: Introductionmentioning

confidence: 99%

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Lipofection of plasmid DNA into human mast cell lines using lipid nanoparticles generated by microfluidic mixing

Duguay

Huang

Kulka

2018

Journal of Leukocyte Biology

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Mast cells are important immune cells that have significant roles in mediating allergy and asthma. Therefore, studying the molecular mechanisms regulating these and other processes in mast cells is important to elucidate. Methods such as lipofection, transduction, and electroporation are often employed to dissect these mechanisms by disrupting gene expression in mast cell lines. However, as with other leukocytes, human mast cells (HMCs) are often refractory to the delivery of plasmids by lipofection. In this study, we investigated the utility of lipid nanoparticles (LNPs) containing the ionizable cationic lipids 1,2-dioleoyloxy-3-dimethylaminopropane, 1,2-dioleyloxy-3-dimethylaminopropane, or 2,2-dilinoleyl-4-(2-dimethylaminoethyl)-[1,3]-dioxolane for the delivery of plasmid DNA into HMC lines. Herein, we demonstrate for the first time the use of LNPs to achieve significant and reproducible levels of plasmid DNA transfection in HMC-1.2 and laboratory of allergic diseases 2 (LAD2) cells. These levels reached 53.2% and 16.0% in HMC-1.2 and LAD2 cells, respectively; and outperformed Lipofectamine 3000 in both cases. Moreover, cell viability in the transfected cells remained above 65% for all LNP conditions tested. Together, these observations illustrate the efficacy of this technique for mast cell researchers and further support the use of LNPs for nucleic acid delivery into leukocytes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Mast Cells Respond To a Variety Of Soluble Mediators Throughmentioning

confidence: 99%

Section: Cells (Comparementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Lipofection of plasmid DNA into human mast cell lines using lipid nanoparticles generated by microfluidic mixing

Duguay

Huang

Kulka

2018

Journal of Leukocyte Biology

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High‐Precision Synthesis of RNA‐Loaded Lipid Nanoparticles for Biomedical Applications

Seo

Jeon

Kwon

et al. 2023

Adv Healthcare Materials

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The recent development of RNA-based therapeutics in delivering nucleic acids for gene editing and regulating protein translation has led to the effective treatment of various diseases including cancer, inflammatory and genetic disorder, as well as infectious diseases. Among these, lipid nanoparticles (LNP) have emerged as a promising platform for RNA delivery and have shed light by resolving the inherent instability issues of naked RNA and thereby enhancing the therapeutic potency. These LNP consisting of ionizable lipid, helper lipid, cholesterol, and poly(ethylene glycol)-anchored lipid can stably enclose RNA and help them release into the cells' cytosol. Herein, the significant progress made in LNP research starting from the LNP constituents, formulation, and their diverse applications is summarized first. Moreover, the microfluidic methodologies which allow precise assembly of these newly developed constituents to achieve LNP with controllable composition and size, high encapsulation efficiency as well as scalable production are highlighted. Furthermore, a short discussion on current challenges as well as an outlook will be given on emerging approaches to resolving these issues.

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Physiological Barriers and Strategies of Lipid‐Based Nanoparticles for Nucleic Acid Drug Delivery

Hu,

Li,

You

et al. 2023

Advanced Materials

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Lipid‐based nanoparticles (LBNPs) are currently the most promising vehicles for nucleic acid drug (NAD) delivery. Although their clinical applications have achieved success, the NAD delivery efficiency and safety are still unsatisfactory, which are, to a large extent, due to the existence of multi‐level physiological barriers in vivo. It is important to elucidate the interactions between these barriers and LBNPs, which will guide more rational design of efficient NAD vehicles with low adverse effects and facilitate broader applications of nucleic acid therapeutics. In this review, we describe the obstacles and challenges of biological barriers to NAD delivery at systemic, organ, sub‐organ, cellular and subcellular levels. We comprehensively review the strategies to overcome these barriers, mainly including physically/chemically engineering LBNPs and directly modifying physiological barriers by auxiliary treatments. We then discuss the potentials and challenges for successful translation of these preclinical studies into the clinic. In the end, we address a forward look at the strategies on manipulating protein corona (PC), which may pull off the trick of overcoming those physiological barriers and significantly improve the efficacy and safety of LBNP‐based NADs delivery.This article is protected by copyright. All rights reserved

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Design of lipid nanoparticles for in vitro and in vivo delivery of plasmid DNA

Cited by 157 publications

References 42 publications

Lipofection of plasmid DNA into human mast cell lines using lipid nanoparticles generated by microfluidic mixing

Lipofection of plasmid DNA into human mast cell lines using lipid nanoparticles generated by microfluidic mixing

High‐Precision Synthesis of RNA‐Loaded Lipid Nanoparticles for Biomedical Applications

Physiological Barriers and Strategies of Lipid‐Based Nanoparticles for Nucleic Acid Drug Delivery

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