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Effective in vivo gene delivery with reduced toxicity, achieved by charge and fatty acid -modified cell penetrating peptide
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Number of Authors: 82017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 17056Article in journal (Refereed) Published
Abstract [en]

Non-viral gene delivery systems have gained considerable attention as a promising alternative to viral delivery to treat diseases associated with aberrant gene expression. However, regardless of extensive research, only a little is known about the parameters that underline in vivo use of the nanoparticle-based delivery vectors. The modest efficacy and low safety of non-viral delivery are the two central issues that need to be addressed. We have previously characterized an efficient cell penetrating peptide, PF14, for in vivo applications. In the current work, we first develop an optimized formulation of PF14/pDNA nanocomplexes, which allows removal of the side-effects without compromising the bioefficacy in vivo. Secondly, based on the physicochemical complex formation studies and biological efficacy assessments, we develop a series of PF14 modifications with altered charge and fatty acid content. We show that with an optimal combination of overall charge and hydrophobicity in the peptide backbone, in vivo gene delivery can be augmented. Further combined with the safe formulation, systemic gene delivery lacking any side effects can be achieved.

Place, publisher, year, edition, pages
2017. Vol. 7, article id 17056
National Category
Bioinformatics and Systems Biology Biomaterials Science
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URN: urn:nbn:se:su:diva-151129DOI: 10.1038/s41598-017-17316-yISI: 000417135200023PubMedID: 29213085OAI: oai:DiVA.org:su-151129DiVA, id: diva2:1173027
Available from: 2018-01-11 Created: 2018-01-11 Last updated: 2018-01-11Bibliographically approved

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Lehto, TönisLangel, Ülo
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