article · 26/11/2012
Flavin Conjugates for Delivery of Peptide Nucleic Acids
Résumé
Oligonucleotides and their analogues, such as peptide nucleic acids (PNAs), can be used in chemical strategies to artificially control gene expression. Inefficient cellular uptake and inappropriate cellular localization still remain obstacles in biological applications, however, especially for PNAs. Here we demonstrate that conjugation of PNAs to flavin resulted in efficient internalization into cells through an endocytic pathway. The flavinPNAs exhibited antisense activity in the sub-micromolar range, in the context of a treatment facilitating endosomal escape. Increased endosomal release of flavin conjugates into the cytoplasm and/or nucleus was shown by chloroquine treatment and alsowhen the flavinPNA was conjugated to rhodamine, a mild photosensitizerupon light irradiation. In conclusion, an isoalloxazine moiety can be used as a carrier and attached to a cargo biomolecule, here a PNA, for internalization and functional cytoplasmic/nuclear delivery. Our findings could be useful for further design of PNAs and other oligonucleotide analogues as potent antisense agents.
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Marlin, F., Simon, P., Bonneau, S., Alberti, P., Cordier, C., Boix, C., Perrouault, L., Fossey, A., Saison-Behmoaras, T., Fontecave, M., & Giovannangeli, C. (2012). Flavin Conjugates for Delivery of Peptide Nucleic Acids. ChemBioChem, 13(17), 2593-2598. https://doi.org/10.1002/cbic.201200505@article{Marlin2012_58,
author = {Marlin, Fanny and Simon, Philippe and Bonneau, Stephanie and Alberti, Patrizia and Cordier, Celine and Boix, Charlotte and Perrouault, Loic and Fossey, Aurelie and Saison-Behmoaras, Tula and Fontecave, Marc and Giovannangeli, Carine},
year = {2012},
month = {11},
title = {Flavin Conjugates for Delivery of Peptide Nucleic Acids},
journal = {ChemBioChem},
volume = {13},
number = {17},
pages = {2593-2598},
abstract = {Oligonucleotides and their analogues, such as peptide nucleic acids (PNAs), can be used in chemical strategies to artificially control gene expression. Inefficient cellular uptake and inappropriate cellular localization still remain obstacles in biological applications, however, especially for PNAs. Here we demonstrate that conjugation of PNAs to flavin resulted in efficient internalization into cells through an endocytic pathway. The flavinPNAs exhibited antisense activity in the sub-micromolar range, in the context of a treatment facilitating endosomal escape. Increased endosomal release of flavin conjugates into the cytoplasm and/or nucleus was shown by chloroquine treatment and alsowhen the flavinPNA was conjugated to rhodamine, a mild photosensitizerupon light irradiation. In conclusion, an isoalloxazine moiety can be used as a carrier and attached to a cargo biomolecule, here a PNA, for internalization and functional cytoplasmic/nuclear delivery. Our findings could be useful for further design of PNAs and other oligonucleotide analogues as potent antisense agents.},
url = {http://www.dx.doi.org/10.1002/cbic.201200505},
doi = {10.1002/cbic.201200505},
issn = {1439-4227},
}TY - JOUR
AU - Marlin, Fanny
AU - Simon, Philippe
AU - Bonneau, Stephanie
AU - Alberti, Patrizia
AU - Cordier, Celine
AU - Boix, Charlotte
AU - Perrouault, Loic
AU - Fossey, Aurelie
AU - Saison-Behmoaras, Tula
AU - Fontecave, Marc
AU - Giovannangeli, Carine
PY - 2012
DA - 2012/11/26
TI - Flavin Conjugates for Delivery of Peptide Nucleic Acids
JO - ChemBioChem
VL - 13
IS - 17
SN - 1439-4227
AB - Oligonucleotides and their analogues, such as peptide nucleic acids (PNAs), can be used in chemical strategies to artificially control gene expression. Inefficient cellular uptake and inappropriate cellular localization still remain obstacles in biological applications, however, especially for PNAs. Here we demonstrate that conjugation of PNAs to flavin resulted in efficient internalization into cells through an endocytic pathway. The flavinPNAs exhibited antisense activity in the sub-micromolar range, in the context of a treatment facilitating endosomal escape. Increased endosomal release of flavin conjugates into the cytoplasm and/or nucleus was shown by chloroquine treatment and alsowhen the flavinPNA was conjugated to rhodamine, a mild photosensitizerupon light irradiation. In conclusion, an isoalloxazine moiety can be used as a carrier and attached to a cargo biomolecule, here a PNA, for internalization and functional cytoplasmic/nuclear delivery. Our findings could be useful for further design of PNAs and other oligonucleotide analogues as potent antisense agents.
SP - 2593
EP - 2598
DO - 10.1002/cbic.201200505
UR - http://www.dx.doi.org/10.1002/cbic.201200505
ER -