Coming in and Finding Out: Blending Receptor-Targeted Delivery and Efficient Endosomal Escape in a Novel Bio-Responsive siRNA Delivery System for Gene Knockdown in Pulmonary T Cells
Identifieur interne : 000941 ( Main/Exploration ); précédent : 000940; suivant : 000942Coming in and Finding Out: Blending Receptor-Targeted Delivery and Efficient Endosomal Escape in a Novel Bio-Responsive siRNA Delivery System for Gene Knockdown in Pulmonary T Cells
Auteurs : Rima Kandil ; Yuran Xie ; Ralf Heermann ; Lorenz Isert ; Kirsten Jung ; Aditi Mehta ; Olivia M. MerkelSource :
- Advanced therapeutics [ 2366-3987 ] ; 2019.
Abstract
RNA interference (RNAi) offers the potential to selectively silence disease-related genes in defined cell subsets. Translation into the clinical routine is, however, still hampered by the lack of efficient carrier systems for therapeutic siRNA, endosomal entrapment presenting a major hurdle. A promising siRNA delivery system has previously been developed on the base of polyethylenimine (PEI) and the targeting ligand transferrin (Tf) to specifically reach activated T cells in the lung. In the present work, the focus is on optimizing Tf-PEI polyplexes for gene knockdown in primary activated T cells by improving their endosomal escape properties. Blending of the conjugate with membrane lytic melittin significantly enhanced endosomal release and thereby cytoplasmic delivery, while maintaining selective T cell targeting abilities and overall cell tolerability. The gathered data furthermore demonstrate that melittin addition also distinctly improves several other essential particle characteristics, such as siRNA encapsulation efficiency and stability in lung lining fluids. In conclusion, this results in a novel upgraded siRNA delivery system that is not only able to specifically deliver its payload to the desired target cells via receptor-mediated endocytosis, but also shows enhanced release from endosomal vesicles in order to initiate RNAi in the cytoplasm.
Url:
DOI: 10.1002/adtp.201900047
PubMed: 31372493
PubMed Central: 6675603
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000387
- to stream Pmc, to step Curation: 000387
- to stream Pmc, to step Checkpoint: 000878
- to stream Ncbi, to step Merge: 000872
- to stream Ncbi, to step Curation: 000872
- to stream Ncbi, to step Checkpoint: 000872
- to stream Main, to step Merge: 000941
- to stream Main, to step Curation: 000941
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Coming in and Finding Out: Blending Receptor-Targeted Delivery and Efficient Endosomal Escape in a Novel Bio-Responsive siRNA Delivery System for Gene Knockdown in Pulmonary T Cells</title><author><name sortKey="Kandil, Rima" sort="Kandil, Rima" uniqKey="Kandil R" first="Rima" last="Kandil">Rima Kandil</name></author><author><name sortKey="Xie, Yuran" sort="Xie, Yuran" uniqKey="Xie Y" first="Yuran" last="Xie">Yuran Xie</name></author><author><name sortKey="Heermann, Ralf" sort="Heermann, Ralf" uniqKey="Heermann R" first="Ralf" last="Heermann">Ralf Heermann</name></author><author><name sortKey="Isert, Lorenz" sort="Isert, Lorenz" uniqKey="Isert L" first="Lorenz" last="Isert">Lorenz Isert</name></author><author><name sortKey="Jung, Kirsten" sort="Jung, Kirsten" uniqKey="Jung K" first="Kirsten" last="Jung">Kirsten Jung</name></author><author><name sortKey="Mehta, Aditi" sort="Mehta, Aditi" uniqKey="Mehta A" first="Aditi" last="Mehta">Aditi Mehta</name></author><author><name sortKey="Merkel, Olivia M" sort="Merkel, Olivia M" uniqKey="Merkel O" first="Olivia M." last="Merkel">Olivia M. Merkel</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31372493</idno><idno type="pmc">6675603</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675603</idno><idno type="RBID">PMC:6675603</idno><idno type="doi">10.1002/adtp.201900047</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000387</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000387</idno><idno type="wicri:Area/Pmc/Curation">000387</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000387</idno><idno type="wicri:Area/Pmc/Checkpoint">000878</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000878</idno><idno type="wicri:Area/Ncbi/Merge">000872</idno><idno type="wicri:Area/Ncbi/Curation">000872</idno><idno type="wicri:Area/Ncbi/Checkpoint">000872</idno><idno type="wicri:Area/Main/Merge">000941</idno><idno type="wicri:Area/Main/Curation">000941</idno><idno type="wicri:Area/Main/Exploration">000941</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Coming in and Finding Out: Blending Receptor-Targeted Delivery and Efficient Endosomal Escape in a Novel Bio-Responsive siRNA Delivery System for Gene Knockdown in Pulmonary T Cells</title><author><name sortKey="Kandil, Rima" sort="Kandil, Rima" uniqKey="Kandil R" first="Rima" last="Kandil">Rima Kandil</name></author><author><name sortKey="Xie, Yuran" sort="Xie, Yuran" uniqKey="Xie Y" first="Yuran" last="Xie">Yuran Xie</name></author><author><name sortKey="Heermann, Ralf" sort="Heermann, Ralf" uniqKey="Heermann R" first="Ralf" last="Heermann">Ralf Heermann</name></author><author><name sortKey="Isert, Lorenz" sort="Isert, Lorenz" uniqKey="Isert L" first="Lorenz" last="Isert">Lorenz Isert</name></author><author><name sortKey="Jung, Kirsten" sort="Jung, Kirsten" uniqKey="Jung K" first="Kirsten" last="Jung">Kirsten Jung</name></author><author><name sortKey="Mehta, Aditi" sort="Mehta, Aditi" uniqKey="Mehta A" first="Aditi" last="Mehta">Aditi Mehta</name></author><author><name sortKey="Merkel, Olivia M" sort="Merkel, Olivia M" uniqKey="Merkel O" first="Olivia M." last="Merkel">Olivia M. Merkel</name></author></analytic><series><title level="j">Advanced therapeutics</title><idno type="eISSN">2366-3987</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">RNA interference (RNAi) offers the potential to selectively silence disease-related genes in defined cell subsets. Translation into the clinical routine is, however, still hampered by the lack of efficient carrier systems for therapeutic siRNA, endosomal entrapment presenting a major hurdle. A promising siRNA delivery system has previously been developed on the base of polyethylenimine (PEI) and the targeting ligand transferrin (Tf) to specifically reach activated T cells in the lung. In the present work, the focus is on optimizing Tf-PEI polyplexes for gene knockdown in primary activated T cells by improving their endosomal escape properties. Blending of the conjugate with membrane lytic melittin significantly enhanced endosomal release and thereby cytoplasmic delivery, while maintaining selective T cell targeting abilities and overall cell tolerability. The gathered data furthermore demonstrate that melittin addition also distinctly improves several other essential particle characteristics, such as siRNA encapsulation efficiency and stability in lung lining fluids. In conclusion, this results in a novel upgraded siRNA delivery system that is not only able to specifically deliver its payload to the desired target cells via receptor-mediated endocytosis, but also shows enhanced release from endosomal vesicles in order to initiate RNAi in the cytoplasm.</p></div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Heermann, Ralf" sort="Heermann, Ralf" uniqKey="Heermann R" first="Ralf" last="Heermann">Ralf Heermann</name><name sortKey="Isert, Lorenz" sort="Isert, Lorenz" uniqKey="Isert L" first="Lorenz" last="Isert">Lorenz Isert</name><name sortKey="Jung, Kirsten" sort="Jung, Kirsten" uniqKey="Jung K" first="Kirsten" last="Jung">Kirsten Jung</name><name sortKey="Kandil, Rima" sort="Kandil, Rima" uniqKey="Kandil R" first="Rima" last="Kandil">Rima Kandil</name><name sortKey="Mehta, Aditi" sort="Mehta, Aditi" uniqKey="Mehta A" first="Aditi" last="Mehta">Aditi Mehta</name><name sortKey="Merkel, Olivia M" sort="Merkel, Olivia M" uniqKey="Merkel O" first="Olivia M." last="Merkel">Olivia M. Merkel</name><name sortKey="Xie, Yuran" sort="Xie, Yuran" uniqKey="Xie Y" first="Yuran" last="Xie">Yuran Xie</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000941 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000941 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= PMC:6675603
|texte= Coming in and Finding Out: Blending Receptor-Targeted Delivery and Efficient Endosomal Escape in a Novel Bio-Responsive siRNA Delivery System for Gene Knockdown in Pulmonary T Cells
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:31372493" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a ChloroquineV1
| This area was generated with Dilib version V0.6.33. |  |