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NickFects, Phosphorylated Derivatives of Transportan 10 for Cellular Delivery of Oligonucleotides
Stockholm University, Faculty of Science, Department of Neurochemistry.ORCID iD: 0000-0001-7746-8574
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2011 (English)In: International journal of peptide research and therapeutics, ISSN 1573-3149, Vol. 17, no 2, 147-157 p.Article in journal (Refereed) Published
Abstract [en]

Oligonucleotide-based gene regulation has a high potential in gene therapy, but the plasma membrane is impermeable for nucleic acid polymers and, consequently, an efficient and non-toxic transfection agent is needed for their delivery into the cell. In this study we present a novel series, NickFects, of chemically modified TP10 peptide-based delivery vectors used for the cellular delivery of single-stranded oligonucleotides. These carriers, obtained by replacement of Ile8 by threonine in stearyl-TP10 and by modifying of tyrosine and/or threonine, respectively, by phosphorylation formed 300-500 nm in size peptide: oligonucleotide nanocomplexes with negative surface charges. The highest splice-correcting effect was obtained when phosphorotiate 2'-O-methyl oligonucleotides were transduced into cells by NickFect1 (NF1) or NickFect2 (NF2). In addition, we also show how a small modification (one or two negative charges) in peptide sequence can affect its ability to deliver ONs into cells and increase their potency in the splicing redirection assay. Our studies demonstrate that NF1 and NF2 have higher transfection efficacy for oligonucleotides as compared to the most commonly used transfection agent Lipofectamine (TM) 2000 and lead to higher biological response in cells.

Place, publisher, year, edition, pages
2011. Vol. 17, no 2, 147-157 p.
Keyword [en]
Cell-penetrating peptide, Splice correction assay, Co-incubation, Stearylation, Phosphorylated peptide, Delivery vector
National Category
Chemical Sciences
URN: urn:nbn:se:su:diva-67581DOI: 10.1007/s10989-011-9252-1ISI: 000293235700009OAI: diva2:470561

authorCount :8

Available from: 2011-12-29 Created: 2011-12-29 Last updated: 2015-04-21Bibliographically approved

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Lindberg, StaffanLangel, Ülo
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