Lipid nanoparticles (LNPs) for in vivo RNA delivery and their breakthrough technology for future applications

Jeong, Michaela; Lee, Yeji; Park, Jeongeun; Jung, Hyein; Lee, Hyukjin

doi:10.1016/j.addr.2023.114990

Cited by 43 publications

(19 citation statements)

References 201 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, passive targeting of RNA-based nanoparticles relies on interactions with serum proteins in endogenous trafficking pathways. Currently, LNPs have demonstrated effective delivery of RNA to the liver through passive cellular targeting by controlling size and protein adsorption. , Furthermore, modifications of the chemical components of LNPs have been investigated to enhance their accumulation in lung and spleen tissues. Typically, by modulating the charge payload of nanoparticles, passive targeting to the spleen can be achieved.…”

Section: Chemical Modification-assisted Better Rna Therapeuticsmentioning

confidence: 99%

Chemically Modified Platforms for Better RNA Therapeutics

Shi,

Zhen,

Zhang

et al. 2024

Chem. Rev.

View full text Add to dashboard Cite

RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential in disease prevention and treatment. However, despite their remarkable achievements, these therapies encounter substantial challenges including low stability, susceptibility to degradation by nucleases, and a prominent negative charge, thereby hindering further development. Chemically modified platforms have emerged as a strategic innovation, focusing on precise alterations either on the RNA moieties or their associated delivery vectors. This comprehensive review delves into these platforms, underscoring their significance in augmenting the performance and translational prospects of RNA-based therapeutics. It encompasses an in-depth analysis of various chemically modified delivery platforms that have been instrumental in propelling RNA therapeutics toward clinical utility. Moreover, the review scrutinizes the rationale behind diverse chemical modification techniques aiming at optimizing the therapeutic efficacy of RNA molecules, thereby facilitating robust disease management. Recent empirical studies corroborating the efficacy enhancement of RNA therapeutics through chemical modifications are highlighted. Conclusively, we offer profound insights into the transformative impact of chemical modifications on RNA drugs and delineates prospective trajectories for their future development and clinical integration. CONTENTS1. Introduction 930 2. Current Status and Challenges of RNA Therapeutics in Clinics 933 2.1. Molecular Mechanisms and Clinical Research Progress of RNAs 934 2.1.1. ASO 934 2.1.2. siRNA 934 2.1.3. Aptamer 936 2.1.4. mRNA 936 2.1.5. RNA Therapeutics on the Cusp of Clinical Breakthroughs 938 2.2. Major Challenges of Current RNA Therapeutics in Clinics 940 2.

show abstract

Section: Chemical Modification-assisted Better Rna Therapeuticsmentioning

confidence: 99%

Chemically Modified Platforms for Better RNA Therapeutics

Shi,

Zhen,

Zhang

et al. 2024

Chem. Rev.

View full text Add to dashboard Cite

show abstract

“…Since the whole-body knockout mouse model demonstrated that miR-26b plays a role in MASH, we attempted to rescue the phenotype by injecting Apoe -/-Mir26b -/mice on WTD with LNPs, which act as clinically and therapeutically relevant vehicles [8], loaded with miR-26b mimics (mLNPs) and empty lipid nanoparticles (eLNPs) as control for 4…”

Section: Lipid Nanoparticles Loaded With Mir-26b Mimics Can Partly Re...mentioning

confidence: 99%

“…In this investigation, we used previously described miR-26b knockout mice [5] and myeloid cell-specific miR-26b knockout mice to clarify the role of miR-26b in hepatic lipid metabolism, inflammation, and fibrogenesis. Furthermore, lipid nanoparticles (LNPs), which act as clinically and therapeutically relevant vehicles [8], loaded with miR-26b mimics were used to restore miR-26b levels in mice as well as in human precision-cut liver slices to investigate its therapeutic potential.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-26b protects against MASH development and can be efficiently targeted with lipid nanoparticles

Peters,

Rakateli,

Huchzermeier

et al. 2024

Preprint

View full text Add to dashboard Cite

Background & AimsThe prevalence of metabolic dysfunction-associated steatohepatitis (MASH) is increasing, urging more research into the underlying mechanisms. MicroRNA-26b (miR-26b) might play a role in several MASH-related pathways. Therefore, we aimed to determine the role of miR-26b in MASH and its therapeutic potential using miR-26b mimic-loaded lipid nanoparticles (LNPs).MethodsApoe-/-Mir26b-/-,Apoe-/-LysMcreMir26bfl/flmice, and respective controls were fed a western-type diet to induce MASH. Plasma and liver samples were characterized regarding lipid metabolism, hepatic inflammation, and fibrosis. Additionally, miR-26b mimic-loaded LNPs were injected inApoe-/-Mir26b-/-mice to rescue the phenotype and key results were validated in human precision-cut liver slices. Finally, kinase profiling was used to elucidate underlying mechanisms.ResultsApoe-/-Mir26b-/-mice showed increased hepatic lipid levels, coinciding with increased expression of scavenger receptor a and platelet glycoprotein 4. Similar effects were found in mice lacking myeloid-specificmiR-26b. Additionally, hepatic TNF and IL-6 levels and amount of infiltrated macrophages were increased inApoe-/-Mir26b-/-mice. Moreover,Tgfbexpression was increased by themiR-26bdeficiency, leading to more hepatic fibrosis. A murine treatment model with miR-26b mimic-loaded LNPs reduced hepatic lipids, rescuing the observed phenotype. Kinase profiling identified increased inflammatory signaling uponmiR-26bdeficiency, which was rescued by LNP treatment. Finally, miR-26b mimic-loaded LNPs also reduced inflammation in human precision-cut liver slices.ConclusionsOverall, our study demonstrates that the detrimental effects ofmiR-26bdeficiency in MASH can be rescued by LNP treatment. This novel discovery leads to more insight into MASH development, opening doors to potential new treatment options using LNP technology.Graphical abstract

show abstract

“…Those LNP systems have provided fundamental knowledge of the LNP drug delivery platform utilizing synthetic chemistry for a better understanding of nucleic acid delivery in vivo . There are quite a few recent important reviews discussing the potential applications and the importance of LNPs, which can be found elsewhere. − Other forms of lipid-based systems such as liposomes with an inner cationic lipid layer and an outer neutral lipid layer, PEG-conjugated lipid-based siRNA carriers, and calcium phosphate core with lipid surrounding, can also successfully deliver RNA for different biomedical applications, which have been summarized elsewhere. ,− …”

Section: Therapeutic Nucleic Acid Delivery Strategiesmentioning

confidence: 99%

Bioinspired Spatiotemporal Management toward RNA Therapies

Ma,

Li,

Lin

et al. 2023

ACS Nano

View full text Add to dashboard Cite

Lipid nanoparticles (LNPs) for in vivo RNA delivery and their breakthrough technology for future applications

Cited by 43 publications

References 201 publications

Chemically Modified Platforms for Better RNA Therapeutics

Chemically Modified Platforms for Better RNA Therapeutics

MicroRNA-26b protects against MASH development and can be efficiently targeted with lipid nanoparticles

Bioinspired Spatiotemporal Management toward RNA Therapies

Contact Info

Product

Resources

About