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Delivery of nucleic...
Delivery of nucleic acids with a stearylated (RxR)4 peptide using a non-covalent co-incubation strategy
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- Lehto, Taavi (author)
- Stockholms universitet,Institutionen för neurokemi,University of Tartu, Estonia
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Abes, Rachida (author)
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Oskolkov, Nikita (author)
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Suhorutšenko, Julia (author)
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Copolovici, Dana-Maria (author)
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- Mäger, Imre (author)
- Stockholms universitet,Institutionen för neurokemi,University of Tartu, Estonia
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Viola, Joana R. (author)
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Simonson, Oscar E. (author)
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- Ezzat, Kariem (author)
- Karolinska Institutet,Stockholms universitet,Institutionen för neurokemi
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- Guterstam, Peter (author)
- Stockholms universitet,Institutionen för neurokemi
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- Eriste, Elo (author)
- Karolinska Institutet
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Smith, Edvard (author)
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Lebleu, Bernard (author)
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- EL Andaloussi, Samir (author)
- Karolinska Institutet,Stockholms universitet,Institutionen för neurokemi,University of Tartu, Estonia
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- Langel, Ülo (author)
- Stockholms universitet,Institutionen för neurokemi,University of Tartu, Estonia
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(creator_code:org_t)
- Elsevier BV, 2010
- 2010
- English.
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In: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 141:1, s. 42-51
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- In recent years, oligonucleotide-based molecules have been intensely used to modulate gene expression. All these molecules share the common feature of being essentially impermeable over cellular membranes and they therefore require efficient delivery vectors. Cell-penetrating peptides are a group of delivery peptides that has been readily used for nucleic acid delivery. In particular, polyarginine and derivates thereof, i.e. the (RxR)4 peptide, have been applied with success both in vitro and in vivo. A major problem, however, with these arginine-rich peptides is that they frequently remain trapped in endosomal compartments following internalization. The activity of polyarginine has previously been improved by conjugation to a stearyl moiety. Therefore, we sought to investigate what impact such modification would have on the pre-clinically used (RxR)4 peptide for non-covalent delivery of plasmids and splice-correcting oligonucleotides (SCOs) and compare it with stearylated Arg9 and Lipofectamine™ 2000. We show that stearyl-(RxR)4 mediates efficient plasmid transfections in several cell lines and the expression levels are significantly higher than when using unmodified (RxR)4 or stearylated Arg9. Although the transfection efficiency is lower than with Lipofectamine™ 2000, we show that stearyl-(RxR)4 is substantially less toxic. Furthermore, using a functional splice-correction assay, we show that stearyl-(RxR)4 complexed with 2′-OMe SCOs promotes significant splice correction whereas stearyl-Arg9 fails to do so. Moreover, stearyl-(RxR)4 promotes dose-dependent splice correction in parity with (RxR)4-PMO covalent conjugates, but at least 10-times lower concentration. These features make this stearic acid modified analog of (RxR)4 an intriguing vector for future in vivo experiments.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Cell-penetrating peptide
- Gene delivery
- Oligonucleotide delivery
- Splice correction
- Stearylation
- Neurochemistry
- Neurokemi
- neurokemi med molekylär neurobiologi
- Neurochemistry with Molecular Neurobiology
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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Abes, Rachida
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Oskolkov, Nikita
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Suhorutšenko, Ju ...
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Copolovici, Dana ...
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Mäger, Imre
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show more...
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Viola, Joana R.
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Simonson, Oscar ...
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Ezzat, Kariem
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Guterstam, Peter
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Eriste, Elo
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Smith, Edvard
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Lebleu, Bernard
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EL Andaloussi, S ...
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Langel, Ülo
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Journal of Contr ...
- By the university
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Stockholm University
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Karolinska Institutet