Search: onr:"swepub:oai:DiVA.org:su-84941" >
Intracellular Deliv...
-
Dash-Wagh, SuvarnaKarolinska Institutet,Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
(author)
Intracellular Delivery of Short Interfering RNA in Rat Organ of Corti Using a Cell-penetrating Peptide PepFect6
- Article/chapterEnglish2012
Publisher, publication year, extent ...
-
Elsevier BV,2012
-
printrdacarrier
Numbers
-
LIBRIS-ID:oai:DiVA.org:su-84941
-
https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-84941URI
-
https://doi.org/10.1038/mtna.2012.50DOI
-
http://kipublications.ki.se/Default.aspx?queryparsed=id:128455841URI
-
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-101047URI
Supplementary language notes
-
Language:English
-
Summary in:English
Part of subdatabase
Classification
-
Subject category:ref swepub-contenttype
-
Subject category:art swepub-publicationtype
Notes
-
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.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
-
Jacob, StefanKarolinska Institutet,Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden
(author)
-
Lindberg, StaffanStockholms universitet,Institutionen för neurokemi,Department of Neurochemistry, Stockholm University, Stockholm, Sweden(Swepub:su)stli4680
(author)
-
Fridberger, Anders,1966-Karolinska Institutet,Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden(Swepub:liu)andfr39
(author)
-
Langel, ÜloStockholms universitet,Institutionen för neurokemi,Department of Neurochemistry, Stockholm University, Stockholm, Sweden(Swepub:su)ulo
(author)
-
Ulfendahl, MatsKarolinska Institutet,Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
(author)
-
Karolinska InstitutetDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden
(creator_code:org_t)
Related titles
-
In:Molecular Therapy Nucleic Acids: Elsevier BV1:e612162-2531
Internet link
Find in a library
To the university's database