In situ T-cell transfection by anti-CD3-conjugated lipid nanoparticles leads to T-cell activation, migration, and phenotypic shift.
Lipid nanoparticle
Reporter gene
T-cell activation
T-cell transfection
mRNA
Journal
Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
17
12
2021
accepted:
24
12
2021
pubmed:
26
1
2022
medline:
14
4
2022
entrez:
25
1
2022
Statut:
ppublish
Résumé
Ex vivo programming of T cells can be efficacious but is complex and expensive; therefore, the development of methods to transfect T cells in situ is important. We developed and optimized anti-CD3-targeted lipid nanoparticles (aCD3-LNPs) to deliver tightly packed, reporter gene mRNA specifically to T cells. In vitro, targeted LNPs efficiently delivered mCherry mRNA to Jurkat T cells, and T-cell activation and depletion were associated with aCD3 antibody coating on the surface of LNPs. aCD3-LNPs, but not non-targeted LNPs, accumulated within the spleen following systemic injection, with mCherry and Fluc signals visible within 30 min after injection. At 24 h after aCD3-LNP injection, 2-4% of all splenic T cells and 2-7% of all circulating T cells expressed mCherry, and this was dependent on aCD3 coating density. Targeting and transfection were accompanied by systemic CD25
Identifiants
pubmed: 35078042
pii: S0142-9612(21)00695-5
doi: 10.1016/j.biomaterials.2021.121339
pmc: PMC8892572
mid: NIHMS1770200
pii:
doi:
Substances chimiques
Lipid Nanoparticles
0
Lipids
0
Liposomes
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
121339Subventions
Organisme : NCI NIH HHS
ID : R01 CA253316
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA210553
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA118681
Pays : United States
Organisme : NIBIB NIH HHS
ID : R01 EB028646
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007276
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA112356
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA124435
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA250557
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
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