Complex Size and Surface Charge Determine Nucleic Acid Transfer by Fusogenic Liposomes
Highly efficient, biocompatible, and fast nucleic acid delivery methods are essential for biomedical applications and research. At present, two main strategies are used to this end. In non-viral transfection liposome- or polymer-based formulations are used to transfer cargo into cells via endocytosi...
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doaj-32abe1cd399746f2ad3698a3b063044e2020-11-25T02:01:59ZengMDPI AGInternational Journal of Molecular Sciences1422-00672020-03-01216224410.3390/ijms21062244ijms21062244Complex Size and Surface Charge Determine Nucleic Acid Transfer by Fusogenic LiposomesMarco Hoffmann0Nils Hersch1Sven Gerlach2Georg Dreissen3Ronald Springer4Rudolf Merkel5Agnes Csiszár6Bernd Hoffmann7Forschungszentrum Jülich, Institute of Biological Information Processing; IBI-2, 52428 Jülich, GermanyForschungszentrum Jülich, Institute of Biological Information Processing; IBI-2, 52428 Jülich, GermanyForschungszentrum Jülich, Institute of Biological Information Processing; IBI-2, 52428 Jülich, GermanyForschungszentrum Jülich, Institute of Biological Information Processing; IBI-2, 52428 Jülich, GermanyForschungszentrum Jülich, Institute of Biological Information Processing; IBI-2, 52428 Jülich, GermanyForschungszentrum Jülich, Institute of Biological Information Processing; IBI-2, 52428 Jülich, GermanyForschungszentrum Jülich, Institute of Biological Information Processing; IBI-2, 52428 Jülich, GermanyForschungszentrum Jülich, Institute of Biological Information Processing; IBI-2, 52428 Jülich, GermanyHighly efficient, biocompatible, and fast nucleic acid delivery methods are essential for biomedical applications and research. At present, two main strategies are used to this end. In non-viral transfection liposome- or polymer-based formulations are used to transfer cargo into cells via endocytosis, whereas viral carriers enable direct nucleic acid delivery into the cell cytoplasm. Here, we introduce a new generation of liposomes for nucleic acid delivery, which immediately fuse with the cellular plasma membrane upon contact to transfer the functional nucleic acid directly into the cell cytoplasm. For maximum fusion efficiency combined with high cargo transfer, nucleic acids had to be complexed and partially neutralized before incorporation into fusogenic liposomes. Among the various neutralization agents tested, small, linear, and positively charged polymers yielded the best complex properties. Systematic variation of liposomal composition and nucleic acid complexation identified surface charge as well as particle size as essential parameters for cargo-liposome interaction and subsequent fusion induction. Optimized protocols were tested for the efficient transfer of different kinds of nucleic acids like plasmid DNA, messenger RNA, and short-interfering RNA into various mammalian cells in culture and into primary tissues.https://www.mdpi.com/1422-0067/21/6/2244fusogenic liposomestransfectionnucleic acid complexationmembrane fusion |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marco Hoffmann Nils Hersch Sven Gerlach Georg Dreissen Ronald Springer Rudolf Merkel Agnes Csiszár Bernd Hoffmann |
spellingShingle |
Marco Hoffmann Nils Hersch Sven Gerlach Georg Dreissen Ronald Springer Rudolf Merkel Agnes Csiszár Bernd Hoffmann Complex Size and Surface Charge Determine Nucleic Acid Transfer by Fusogenic Liposomes International Journal of Molecular Sciences fusogenic liposomes transfection nucleic acid complexation membrane fusion |
author_facet |
Marco Hoffmann Nils Hersch Sven Gerlach Georg Dreissen Ronald Springer Rudolf Merkel Agnes Csiszár Bernd Hoffmann |
author_sort |
Marco Hoffmann |
title |
Complex Size and Surface Charge Determine Nucleic Acid Transfer by Fusogenic Liposomes |
title_short |
Complex Size and Surface Charge Determine Nucleic Acid Transfer by Fusogenic Liposomes |
title_full |
Complex Size and Surface Charge Determine Nucleic Acid Transfer by Fusogenic Liposomes |
title_fullStr |
Complex Size and Surface Charge Determine Nucleic Acid Transfer by Fusogenic Liposomes |
title_full_unstemmed |
Complex Size and Surface Charge Determine Nucleic Acid Transfer by Fusogenic Liposomes |
title_sort |
complex size and surface charge determine nucleic acid transfer by fusogenic liposomes |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2020-03-01 |
description |
Highly efficient, biocompatible, and fast nucleic acid delivery methods are essential for biomedical applications and research. At present, two main strategies are used to this end. In non-viral transfection liposome- or polymer-based formulations are used to transfer cargo into cells via endocytosis, whereas viral carriers enable direct nucleic acid delivery into the cell cytoplasm. Here, we introduce a new generation of liposomes for nucleic acid delivery, which immediately fuse with the cellular plasma membrane upon contact to transfer the functional nucleic acid directly into the cell cytoplasm. For maximum fusion efficiency combined with high cargo transfer, nucleic acids had to be complexed and partially neutralized before incorporation into fusogenic liposomes. Among the various neutralization agents tested, small, linear, and positively charged polymers yielded the best complex properties. Systematic variation of liposomal composition and nucleic acid complexation identified surface charge as well as particle size as essential parameters for cargo-liposome interaction and subsequent fusion induction. Optimized protocols were tested for the efficient transfer of different kinds of nucleic acids like plasmid DNA, messenger RNA, and short-interfering RNA into various mammalian cells in culture and into primary tissues. |
topic |
fusogenic liposomes transfection nucleic acid complexation membrane fusion |
url |
https://www.mdpi.com/1422-0067/21/6/2244 |
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