ArticleBiomacromolecules2022
Fingolimod-Conjugated Charge-Altering Releasable Transporters Efficiently and Specifically Deliver mRNA to Lymphocytes In Vivo and In Vitro.
Article in Biomacromolecules, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 11 citations in OpenAlex.
- Article
- Review
- Organ- and Cell-Selective Delivery of mRNA In Vivo Using Guanidinylated Serinol Charge-Altering Releasable Transporters.Journal of the American Chemical Society · 2024Article
- mRNA Delivery: Challenges and Advances through Polymeric Soft Nanoparticles.International journal of molecular sciences · 2024Review
- Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies.Theranostics · 2024Article
- Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism.Nature communications · 2023Article
- mRNA nanodelivery systems: targeting strategies and administration routes.Biomaterials research · 2023Review
- Nanoparticle-Based Chimeric Antigen Receptor Therapy for Cancer Immunotherapy.Tissue engineering and regenerative medicine · 2023Review
- Lysine-Derived Charge-Altering Releasable Transporters: Targeted Delivery of mRNA and siRNA to the Lungs.Bioconjugate chemistry · 2023Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Charge-altering releasable transporters (CARTs) are a class of oligonucleotide delivery vehicles shown to be effective for delivery of messenger RNA (mRNA) both in vitro and in vivo. Here, we exploited the chemical versatility of the CART synthesis to generate CARTs containing the small-molecule drug fingolimod (FTY720) as a strategy to increase mRNA delivery and expression in lymphocytes through a specific ligand-receptor interaction. Fingolimod is an FDA-approved small-molecule drug that, upon in vivo phosphorylation, binds to the sphingosine-1-phosphate receptor 1 (S1P1), which is highly expressed on lymphocytes. Compared to its non-fingolimod-conjugated analogue, the fingolimod-conjugated CART achieved superior transfection of activated human and murine T and B lymphocytes in vitro. The higher transfection of the fingolimod-conjugated CARTs was lost when cells were exposed to a free fingolimod before transfection. In vivo, the fingolimod-conjugated CART showed increased mRNA delivery to marginal zone B cells and NK cells in the spleen, relative to CARTs lacking fingolimod. Moreover, fingolimod-CART-mediated mRNA delivery induces peripheral blood T-cell depletion similar to free fingolimod. Thus, we show that functionalization of CARTs with a pharmacologically validated small molecule can increase transfection of a cellular population of interest while conferring some of the targeting properties of the conjugated small molecule to the CARTs.
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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.