Application of TAL effectors to control gene expression in human cells
Final Report Abstract
In this project, we studied the application potential of artificially engineered transcription activator-like effector proteins (TALEs) in human cells. Studying two promoters of high biomedical importance, the interferon beta (IFN-beta) promoter and the promoter of human immunodeficiency virus (HIV-1), we demonstrated that designed TALEs that bind to defined areas of these promoters are capable to specifically and significantly purge gene expression. Thus, engineered TALEs were shown to considerably induce IFN-beta expression and - signaling in human cells. Applying the hepatitis C virus replicon system, the TALE mediated IFN-beta signaling was demonstrated to bypass pathogen pattern recognition and to effectively prohibit viral RNA replication. Using customized, engineered TALEs and newly established retroviral TALE-expression systems, we showed a substantial transcription activation of integrated HIV provirus and viral outgrowth with cells obtained from different HIV-1 patients. In contrast to latency-reversing agents (LRAs), the TALEs enabled a provirus-specific and patient-adapted induction of HIV transcription. TALES were hence suggested to be potentially useful tools in (i) applications addressing virus-host interactions and (ii) strategies aimed at removing HIV-1 reservoirs.
Publications
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(2014). Antiviral interferon-beta signaling induced by designed transcription activator-like effectors (TALE). PLoSOne 9, e114288
Renner I, Funk N, Geissler R, Penzel A, and Behrens SE
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(2015). Patientadapted, specific activation of HIV-1 by customized TAL effectors (TALEs), a proof of principle study. Virology 486, 248-254
Geissler R, Hauber I, Funk N, Richter AK, Behrens M, Renner I, Chemnitz J, Hofmann- Sieber H, Baum H, van Lunzen J, Boch J, Hauber J, and Behrens SE
