ArticleMolecular therapy. Nucleic acids2025
Albumin-binding dendritic siRNA improves delivery and efficacy to solid tumors in a melanoma model.
Article in Molecular therapy. Nucleic acids, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Albumin-binding dendrimer-conjugated siRNA enables safe and effective gene silencing throughout the central nervous system.Nucleic acids research · 2026Article
- Investigating theBioconjugate chemistry · 2026Article
- 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
- Dendritic siRNA conjugate riding albumin for targeted delivery to solid tumors.Molecular therapy. Nucleic acids · 2025Article
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10 authors.
Funding
Abstract
Small interfering RNA (siRNA) therapeutics are a new class of drugs that is rapidly expanding to tackle various diseases. Extrahepatic delivery of siRNAs, especially to the parenchyma of solid tumors, is challenging with multiple strategies being explored such as lipid nanoparticle based delivery and ligand conjugation strategies. Here, we report that an albumin-binding dendritic siRNA (D-siRNA) boosts blood circulation time following systemic administration, leading to improved delivery and silencing activity in a melanoma tumor model, in comparison to non-albumin binding lipophilic siRNAs. D-siRNAs increased the tumor-to-liver delivery ratio, including both immune and non-immune cell types within the tumor parenchyma. Using D-siRNAs to target JAK1 expression as an adjuvant to immune checkpoint inhibitors, we found that D-siRNAs was able to enhance PD1 antibody treatment and slow tumor progression of melanoma. Thus, this work demonstrates the utility of D-siRNAs as a systemically administered tumor delivery strategy, enabling the use of siRNAs as chemotherapeutic agents. Further mechanistic studies into the role of JAK1 in melanoma pathology and progression may expand this into additional targets as potential treatments.
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Registered trials
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