Unknown

Dataset Information

0

MRNA Polyplexes with Post-Conjugated GALA Peptides Efficiently Target, Transfect, and Activate Antigen Presenting Cells.


ABSTRACT: Vaccines based on mRNA have emerged as potent systems to elicit CD8+ T cell responses against various cancers and viral infectious diseases. The efficient intracellular delivery of mRNA molecules encoding antigens into the cytosol of antigen-presenting cells (APCs) is still challenging, requiring cell attachment, active uptake, and subsequent endosomal escape. Here, we report a facile approach for the formulation of peptide-functionalized mRNA polyplexes using copper-free click chemistry to promote presentation of mRNA antigen by dendritic cells (DCs). After screening different membrane active peptides, GALA modified mRNA polyplexes (PPx-GALA) with a size around 350 nm and with a slightly negative surface charge (-7 mV), exhibited the highest EGFP-mRNA transfection in RAW 246.7 macrophages (?36%) and D1 dendritic cells (?50%) as compared to polyplexes decorated with melittin or LEDE peptides. Interestingly, we found that PPx-GALA enters DCs through sialic acid mediated endo/phagocytosis, which was not influenced by DC maturation. The PPx-GALA formulation exhibited 18-fold higher cellular uptake compared to a lipofectamine mRNA formulation without inducing cytotoxicity. Live cell imaging showed that PPx-GALA that were taken up by endocytosis induced calcein release from endosomes into the cytosol. DCs treated with PPx-GALA containing mRNA encoding for OVA displayed enhanced T cell responses and DC maturation. Collectively, these data provide a strong rationale for further study of this PPx-GALA formulation in vivo as a promising mRNA vaccine platform.

SUBMITTER: Lou B 

PROVIDER: S-EPMC6385079 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

mRNA Polyplexes with Post-Conjugated GALA Peptides Efficiently Target, Transfect, and Activate Antigen Presenting Cells.

Lou Bo B   De Koker Stefaan S   Lau Chun Yin Jerry CYJ   Hennink Wim E WE   Mastrobattista Enrico E  

Bioconjugate chemistry 20181002 2


Vaccines based on mRNA have emerged as potent systems to elicit CD8<sup>+</sup> T cell responses against various cancers and viral infectious diseases. The efficient intracellular delivery of mRNA molecules encoding antigens into the cytosol of antigen-presenting cells (APCs) is still challenging, requiring cell attachment, active uptake, and subsequent endosomal escape. Here, we report a facile approach for the formulation of peptide-functionalized mRNA polyplexes using copper-free click chemis  ...[more]

Similar Datasets

| S-EPMC6861565 | biostudies-literature
| S-EPMC6404535 | biostudies-literature
| S-EPMC6604415 | biostudies-literature
| S-EPMC8047430 | biostudies-literature
| S-EPMC5842139 | biostudies-literature
2004-09-30 | GSE702 | GEO
| S-EPMC3305810 | biostudies-literature
| S-EPMC4722243 | biostudies-literature
| S-EPMC4670273 | biostudies-literature
| S-EPMC7490222 | biostudies-literature