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Lentiviral Protein Transduction with Genome-Modifying HIV-1 Integrase-I-PpoI Fusion Proteins : Studies on Specificity and Cytotoxicity
Joint Authors
Timonen, Oskari
Lesch, Hanna P.
Ylä-Herttuala, Seppo
Schenkwein, Diana
Turkki, Vesa
Husso, Tiia
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-04-20
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Rare-cutting endonucleases, such as the I-PpoI, can be used for the induction of double strand breaks (DSBs) in genome editing and targeted integration based on homologous recombination.
For therapeutic approaches, the specificity and the pattern of off-target effects are of high importance in these techniques.
For its applications, the endonuclease needs to be transported into the target cell nucleus, where the mechanism of transport may affect its function.
Here, we have studied the lentiviral protein transduction of the integrase (IN)-PpoI fusion protein using the cis-packaging method.
In genome-wide interaction studies, IN-fusion proteins were verified to bind their target sequence containing 28S ribosomal RNA (rRNA) genes with a 100-fold enrichment, despite the well-documented behavior of IN to be tethered into various genomic areas by host-cell factors.
In addition, to estimate the applicability of the method, DSB-induced cytotoxic effects with different vector endonuclease configurations were studied in a panel of cells.
Varying the amount and activity of endonuclease enabled the adjustment of ratio between the induced DSBs and transported DNA.
In cell studies, certain cancerous cell lines were especially prone to DSBs in rRNA genes, which led us to test the protein transduction in a tumour environment in an in vivo study.
In summary, the results highlight the potential of lentiviral vectors (LVVs) for the nuclear delivery of endonucleases.
American Psychological Association (APA)
Turkki, Vesa& Schenkwein, Diana& Timonen, Oskari& Husso, Tiia& Lesch, Hanna P.& Ylä-Herttuala, Seppo. 2014. Lentiviral Protein Transduction with Genome-Modifying HIV-1 Integrase-I-PpoI Fusion Proteins : Studies on Specificity and Cytotoxicity. BioMed Research International،Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-467400
Modern Language Association (MLA)
Turkki, Vesa…[et al.]. Lentiviral Protein Transduction with Genome-Modifying HIV-1 Integrase-I-PpoI Fusion Proteins : Studies on Specificity and Cytotoxicity. BioMed Research International No. 2014 (2014), pp.1-11.
https://search.emarefa.net/detail/BIM-467400
American Medical Association (AMA)
Turkki, Vesa& Schenkwein, Diana& Timonen, Oskari& Husso, Tiia& Lesch, Hanna P.& Ylä-Herttuala, Seppo. Lentiviral Protein Transduction with Genome-Modifying HIV-1 Integrase-I-PpoI Fusion Proteins : Studies on Specificity and Cytotoxicity. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-467400
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-467400