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A Peptide-based Vec...
A Peptide-based Vector for Efficient Gene Transfer In Vitro and In Vivo
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- Lehto, Taavi (author)
- Stockholms universitet,Institutionen för neurokemi
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Simonson, Oscar E. (author)
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- Mäger, Imre (author)
- Stockholms universitet,Institutionen för neurokemi
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- Ezzat, Kariem (author)
- Karolinska Institutet,Stockholms universitet,Institutionen för neurokemi
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Sork, Helena (author)
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Copolovici, Dana-Maria (author)
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Viola, Joana R. (author)
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- Zaghloul, Eman M. (author)
- Karolinska Institutet
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Lundin, Per (author)
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Moreno, Pedro M. D. (author)
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- Mäe, Maarja (author)
- Stockholms universitet,Institutionen för neurokemi
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Oskolkov, Nikita (author)
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Suhorutšenko, Julia (author)
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- Smith, C. I. Edvard (author)
- Karolinska Institutet
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- EL Andaloussi, Samir (author)
- Karolinska Institutet
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(creator_code:org_t)
- Elsevier BV, 2011
- 2011
- English.
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In: Molecular Therapy. - : Elsevier BV. - 1525-0016 .- 1525-0024. ; 19:8, s. 1457-1467
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
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- Finding suitable nonviral delivery vehicles for nucleic acid-based therapeutics is a landmark goal in gene therapy. Cell-penetrating peptides (CPPs) are one class of delivery vectors that has been exploited for this purpose. However, since CPPs use endocytosis to enter cells, a large fraction of peptides remain trapped in endosomes. We have previously reported that stearylation of amphipathic CPPs, such as transportan 10 (TP10), dramatically increases transfection of oligonucleotides in vitro partially by promoting endosomal escape. Therefore, we aimed to evaluate whether stearyl-TP10 could be used for the delivery of plasmids as well. Our results demonstrate that stearyl-TP10 forms stable nanoparticles with plasmids that efficiently enter different cell-types in a ubiquitous manner, including primary cells, resulting in significantly higher gene expression levels than when using stearyl-Arg9 or unmodified CPPs. In fact, the transfection efficacy of stearyl-TP10 almost reached the levels of Lipofectamine 2000 (LF2000), however, without any of the observed lipofection-associated toxicities. Most importantly, stearyl-TP10/plasmid nanoparticles are nonimmunogenic, mediate efficient gene delivery in vivo, when administrated intramuscularly (i.m.) or intradermally (i.d.) without any associated toxicity in mice.
Subject headings
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Lehto, Taavi
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Simonson, Oscar ...
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Mäger, Imre
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Ezzat, Kariem
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Sork, Helena
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Copolovici, Dana ...
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show more...
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Viola, Joana R.
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Zaghloul, Eman M ...
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Lundin, Per
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Moreno, Pedro M. ...
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Mäe, Maarja
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Oskolkov, Nikita
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Suhorutšenko, Ju ...
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Smith, C. I. Edv ...
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EL Andaloussi, S ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Chemical Science ...
- Articles in the publication
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Molecular Therap ...
- By the university
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Stockholm University
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Karolinska Institutet