ReviewBioengineering & translational medicine2021
Cytosolic delivery of nucleic acids: The case of ionizable lipid nanoparticles.
Review in Bioengineering & translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers.
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Who cites it
167 citing papers in PubMed.
- Lipid nanoparticles optimized for large RNA cargo and tissue targeting enhance in vivo genome editing.Nature biotechnology · 2026Article
- Structural evolution of ionizable lipids for nucleic acid delivery.Nature reviews. Chemistry · 2026Review
- Design and development of lipid nanoparticle formulations for brain gene therapy.Molecular therapy. Nucleic acids · 2026Article
- Charge-switching ionizable lipids lower the toxicity of lipid nanoparticles.Nature nanotechnology · 2026Article
- Harnessing the endosomal escape compartment as a strategy to enhance RNA delivery via lipid nanoparticles.Molecular therapy. Nucleic acids · 2026Article
- Lipid nanoparticles as active biointerfaces: From membrane interaction to systemic dysregulation.Acta pharmaceutica Sinica. B · 2026Review
- Beyond Metabolism: Pyruvate Carboxylase Acts as a Sequence-Selective Small RNA Sensor Orchestrating Antiviral Responses.bioRxiv : the preprint server for biology · 2026Article
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- Optimized Lipid Nanoparticles with Tail-Modified Ionizable Lipids for Safer mRNA Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Minicircle DNA Vaccines: Overcoming Delivery and Expression Barriers in Next-Generation Immunization.Vaccines · 2026Review
- In Vivo mRNA-Lipid Nanoparticle CAR-T Cell Engineering: Advances, Challenges, and Clinical Translation.Biomedicines · 2026Review
- Localized NF-κB Inhibition Reduces Lipid Nanoparticle-Associated Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Enhanced endosomal escape for nanoparticle-enabled co-delivery of doxorubicin and siRNA to overcome multidrug resistance.Materials today. Advances · 2026Article
- Nanomedicines for DNA and interference RNA co-delivery: Combined gene therapy for Fabry disease.International journal of pharmaceutics: X · 2026Article
- Tissue-specific gene delivery approaches.Bioengineering & translational medicine · 2026Review
- Humanized extracellular vesicles for efficient RNA delivery.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Thioester-Containing Ionizable Lipids with Enhanced Endosomal Escape and Biodegradability for mRNA and tRNA Delivery.Pharmaceutics · 2026Article
- Mechanistic insights into mRNA-LNP interactions: role of ionizable lipid content in regulating mRNA intracellular release and translation.Journal of nanobiotechnology · 2026Article
- In vivo CAR-T therapy: from molecular design to precision delivery.Journal of nanobiotechnology · 2026Review
- Lipid-based nanosystems for atherosclerosis treatment: Evolving approaches and novel therapeutic strategies.Acta pharmaceutica Sinica. B · 2026Review
107 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ionizable lipid nanoparticles (LNPs) are the most clinically advanced nano-delivery system for therapeutic nucleic acids. The great effort put in the development of ionizable lipids with increased in vivo potency brought LNPs from the laboratory benches to the FDA approval of patisiran in 2018 and the ongoing clinical trials for mRNA-based vaccines against SARS-CoV-2. Despite these success stories, several challenges remain in RNA delivery, including what is known as "endosomal escape." Reaching the cytosol is mandatory for unleashing the therapeutic activity of RNA molecules, as their accumulation in other intracellular compartments would simply result in efficacy loss. In LNPs, the ability of ionizable lipids to form destabilizing non-bilayer structures at acidic pH is recognized as the key for endosomal escape and RNA cytosolic delivery. This is motivating a surge in studies aiming at designing novel ionizable lipids with improved biodegradation and safety profiles. In this work, we describe the journey of RNA-loaded LNPs across multiple intracellular barriers, from the extracellular space to the cytosol. In silico molecular dynamics modeling, in vitro high-resolution microscopy analyses, and in vivo imaging data are systematically reviewed to distill out the regulating mechanisms underlying the endosomal escape of RNA. Finally, a comparison with strategies employed by enveloped viruses to deliver their genetic material into cells is also presented. The combination of a multidisciplinary analytical toolkit for endosomal escape quantification and a nature-inspired design could foster the development of future LNPs with improved cytosolic delivery of nucleic acids.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.