ArticleNature communications2024
Structural optimization of siRNA conjugates for albumin binding achieves effective MCL1-directed cancer therapy.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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
26 citing papers in PubMed, 39 citations in OpenAlex.
- Evaluating the effects of aging on distribution and gene silencing activity of lipid-siRNA conjugates delivered into cerebrospinal fluid.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Linker-directed lipid-antigen conjugates co-enhance lymph node targeting and antigen presentation for potent T cell immunity.Materials today. Bio · 2026Article
- The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026Review
- Fatty Acids in Cancer Therapy: Chemical Conjugates, Nanocarriers, and Therapeutic Opportunities.Molecules (Basel, Switzerland) · 2026Review
- Therapeutic delivery of albumin-binding siRNA targeting IRS2 to diverse cell types reduces mammary tumor growth.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Human Serum Albumin as a Prodrug Carrier for Tumor Therapy: Mechanisms, Applications, and Future Perspectives.Pharmaceutics · 2026Review
- Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system.Advanced drug delivery reviews · 2026Review
- Mechanical mechanics-reclaiming a new battlefield for chronic liver disease.Journal of advanced research · 2026Review
- Harnessing albumin's natural tumor-targeting properties: nanoplatform strategies for triple-negative breast cancer therapy.Discover nano · 2026Review
- Targeted Nanocomplex Delivery for Protecting Vascular Integrity and Enhancing Anticancer Effects in Hepatocellular Carcinoma.Small science · 2026Article
- Latest advances in nanodrug delivery systems for modulating the immune microenvironment in triple-negative breast cancer.Frontiers in immunology · 2026Review
- Evaluating the effects of aging on biodistribution and gene silencing activity of lipid-siRNA conjugates delivered into cerebrospinal fluid.bioRxiv : the preprint server for biology · 2025Article
- Intravenous lipid-siRNA conjugate mediates gene silencing at the blood-brain barrier and blood-CSF barrier.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Potentiating cancer immunotherapies with modular albumin-hitchhiking nanobody-STING agonist conjugates.Nature biomedical engineering · 2025Article
- Albumin-binding dendritic siRNA improves delivery and efficacy to solid tumors in a melanoma model.Molecular therapy. Nucleic acids · 2025Article
- siRNA conjugate with high albumin affinity and degradation resistance for delivery and treatment of arthritis in mice and guinea pigs.Nature biomedical engineering · 2025Article
- Advances in locally administered nucleic acid therapeutics.Bioactive materials · 2025Review
- KRAS mutation-driven enhanced macropinocytosis: using albumin as a trojan horse for delivering nanomedicine.Nanomedicine (London, England) · 2025Review
- Elucidating brain transport pathways and cell type-dependent gene silencing of a durable lipid-siRNA conjugate administered into cerebrospinal fluid.Nucleic acids research · 2025Article
- Modulation of TTR gene expression in the eye using modified siRNAs.Nucleic acids research · 2025Article
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Authors and funding
22 authors at 2 institutions in 1 country.
Funding
Abstract
The high potential of siRNAs to silence oncogenic drivers remains largely untapped due to the challenges of tumor cell delivery. Here, divalent lipid-conjugated siRNAs are optimized for in situ binding to albumin to improve pharmacokinetics and tumor delivery. Systematic variation of the siRNA conjugate structure reveals that the location of the linker branching site dictates tendency toward albumin association versus self-assembly, while the lipid hydrophobicity and reversibility of albumin binding also contribute to siRNA intracellular delivery. The lead structure increases tumor siRNA accumulation 12-fold in orthotopic triple negative breast cancer (TNBC) tumors over the parent siRNA. This structure achieves approximately 80% silencing of the anti-apoptotic oncogene MCL1 and yields better survival outcomes in three TNBC models than an MCL-1 small molecule inhibitor. These studies provide new structure-function insights on siRNA-lipid conjugate structures that are intravenously injected, associate in situ with serum albumin, and improve pharmacokinetics and tumor treatment efficacy.
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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.