Fingolimod-Conjugated Charge-Altering Releasable Transporters Efficiently and Specifically Deliver mRNA to Lymphocytes In Vivo and In Vitro.

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. Th

SUBMITTER: Testa S 

PROVIDER: S-EPMC10199726 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature