ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 619 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
619 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,164 citations in OpenAlex.
- Development of siRNA therapeutics to combat microbial infections: a bibliometric analysis.Frontiers in cellular and infection microbiology · 2025Pooled it
- Targeting strategies with lipid vectors for nucleic acid supplementation therapy in Fabry disease: a systematic review.Drug delivery and translational research · 2024Pooled it
- Lipid nanoparticles with aptamers enable targeted mRNA delivery to CD4⁺ T cells.Drug delivery · 2026Article
- Targeted delivery of mRNA to immune cells forDrug delivery · 2026Review
- Novel lipid nanoparticle in a mRNA cancer vaccine drives tumor control via type I IFNs and effector CD8Molecular therapy. Nucleic acids · 2026Article
- Surface charge of LNP and V-ATPase activity of target cell synergize in functional delivery of nucleic acidInternational journal of pharmaceutics: X · 2026Article
- Engineering lipid nanoparticle surface hydrophobicity to modulate nano-bio interface and enable tissue-selective mRNA delivery.Biomaterials · 2026Article
- Cancer nanomedicine and RNA/Lipid nanoparticle platforms in oncology: developmental evolution, translational barriers, and precision-therapy opportunities.Journal of the Egyptian National Cancer Institute · 2026Review
- Balancing stability and cellular interaction in surface-engineered small extracellular vesicles for pulmonary delivery.Materials today. Bio · 2026Article
- Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026Review
- Review
- Focused Ultrasound is Poised to Take Non-Viral Gene Therapies to the Blood-Brain Barrier - and Beyond.Cell biomaterials · 2026Article
- Physiologically based pharmacokinetic modeling of mRNA therapeutics: A multiscale framework for LNP and antibody trafficking in mice.Molecular therapy. Nucleic acids · 2026Article
- Design and development of lipid nanoparticle formulations for brain gene therapy.Molecular therapy. Nucleic acids · 2026Article
- Preparation of placenta-tropic mRNA lipid nanoparticles for pregnancy disorders.Nature protocols · 2026Review
- Advances in vehicles for in situ delivery: From classical vectors to biologically inspired structures.Synthetic and systems biotechnology · 2026Review
- Beyond the genetic code: orchestrating epigenetic and immune landscapes with multivalent mRNA-exosome vaccines.Precision clinical medicine · 2026Review
- Review
- Lipid Nanoparticles for Gene Therapy: Unresolved Challenges in Manufacturing, Transdermal Delivery, Machine Learning, Endosomal Escape, and the Protein Corona.Pharmaceutics · 2026Review
- Lipid nanoparticle delivery of antisense gapmers attenuates pathology in a mouse model of facioscapulohumeral muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
559 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipid nanoparticles (LNPs) have proven to be highly efficient carriers of short-interfering RNAs (siRNAs) to hepatocytes in vivo; however, the precise mechanism by which this efficient delivery occurs has yet to be elucidated. We found that apolipoprotein E (apoE), which plays a major role in the clearance and hepatocellular uptake of physiological lipoproteins, also acts as an endogenous targeting ligand for ionizable LNPs (iLNPs), but not cationic LNPs (cLNPs). The role of apoE was investigated using both in vitro studies employing recombinant apoE and in vivo studies in wild-type and apoE(-/-) mice. Receptor dependence was explored in vitro and in vivo using low-density lipoprotein receptor (LDLR(-/-))-deficient mice. As an alternative to endogenous apoE-based targeting, we developed a targeting approach using an exogenous ligand containing a multivalent N-acetylgalactosamine (GalNAc)-cluster, which binds with high affinity to the asialoglycoprotein receptor (ASGPR) expressed on hepatocytes. Both apoE-based endogenous and GalNAc-based exogenous targeting appear to be highly effective strategies for the delivery of iLNPs to liver.
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Registered trials
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.