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Intracellular Deliv...
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Dash-Wagh, SuvarnaKarolinska Institutet,Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
(författare)
Intracellular Delivery of Short Interfering RNA in Rat Organ of Corti Using a Cell-penetrating Peptide PepFect6
- Artikel/kapitelEngelska2012
Förlag, utgivningsår, omfång ...
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Elsevier BV,2012
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:su-84941
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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-84941URI
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https://doi.org/10.1038/mtna.2012.50DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:128455841URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-101047URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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RNA interference (RNAi) using short interfering RNA (siRNA) is an attractive therapeutic approach for treatment of dominant-negative mutations. Some rare missense dominant-negative mutations lead to congenital-hearing impairments. A variety of viral vectors have been tested with variable efficacy for modulating gene expression in inner ear. However, there is concern regarding their safety for clinical use. Here, we report a novel cell-penetrating peptide (CPP)-based nonviral approach for delivering siRNA into inner ear tissue using organotypic cultures as model system. PepFect6 (PF6), a variant of stearyl-TP10, was specially designed for improved delivery of siRNA by facilitating endosomal release. We show that PF6 was internalized by all cells without inducing cytotoxicity in cochlear cultures. PF6/siRNA nanoparticles lead to knockdown of target genes, a housekeeping gene and supporting cell-specific connexin 26. Interestingly, application of PF6/connexin 26 siRNA exhibited knockdown of both connexin 26 and 30 mRNA and their absence led to impaired intercellular communication as demonstrated by reduced transfer of calcein among the PF6/connexin 26-siRNA-treated cells. Thus, we conclude that PF6 is an efficient nonviral vector for delivery of siRNA, which can be applied as a tool for the development of siRNA-based therapeutic applications for hearing impairments.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Jacob, StefanKarolinska Institutet,Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden
(författare)
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Lindberg, StaffanStockholms universitet,Institutionen för neurokemi,Department of Neurochemistry, Stockholm University, Stockholm, Sweden(Swepub:su)stli4680
(författare)
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Fridberger, Anders,1966-Karolinska Institutet,Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden(Swepub:liu)andfr39
(författare)
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Langel, ÜloStockholms universitet,Institutionen för neurokemi,Department of Neurochemistry, Stockholm University, Stockholm, Sweden(Swepub:su)ulo
(författare)
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Ulfendahl, MatsKarolinska Institutet,Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
(författare)
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Karolinska InstitutetDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Molecular Therapy Nucleic Acids: Elsevier BV1:e612162-2531
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