2.50
Hdl Handle:
http://hdl.handle.net/10033/610428
Title:
Composing a Tumor Specific Bacterial Promoter.
Authors:
Deyneko, Igor V; Kasnitz, Nadine; Leschner, Sara; Weiss, Siegfried ( 0000-0002-5276-8658 )
Abstract:
Systemically applied Salmonella enterica spp. have been shown to invade and colonize neoplastic tissues where it retards the growth of many tumors. This offers the possibility to use the bacteria as a vehicle for the tumor specific delivery of therapeutic molecules. Specificity of such delivery is solely depending on promoter sequences that control the production of a target molecule. We have established the functional structure of bacterial promoters that are transcriptionally active exclusively in tumor tissues after systemic application. We observed that the specific transcriptional activation is accomplished by a combination of a weak basal promoter and a strong FNR binding site. This represents a minimal set of control elements required for such activation. In natural promoters, additional DNA remodeling elements are found that alter the level of transcription quantitatively. Inefficiency of the basal promoter ensures the absence of transcription outside tumors. As a proof of concept, we compiled an artificial promoter sequence from individual motifs representing FNR and basal promoter and showed specific activation in a tumor microenvironment. Our results open possibilities for the generation of promoters with an adjusted level of expression of target proteins in particular for applications in bacterial tumor therapy.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Composing a Tumor Specific Bacterial Promoter. 2016, 11 (5):e0155338 PLoS ONE
Journal:
PloS one
Issue Date:
2016
URI:
http://hdl.handle.net/10033/610428
DOI:
10.1371/journal.pone.0155338
PubMed ID:
27171245
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
publications of the research group molecular Immunology (MOLI)

Full metadata record

DC FieldValue Language
dc.contributor.authorDeyneko, Igor Ven
dc.contributor.authorKasnitz, Nadineen
dc.contributor.authorLeschner, Saraen
dc.contributor.authorWeiss, Siegfrieden
dc.date.accessioned2016-05-20T14:39:17Zen
dc.date.available2016-05-20T14:39:17Zen
dc.date.issued2016en
dc.identifier.citationComposing a Tumor Specific Bacterial Promoter. 2016, 11 (5):e0155338 PLoS ONEen
dc.identifier.issn1932-6203en
dc.identifier.pmid27171245en
dc.identifier.doi10.1371/journal.pone.0155338en
dc.identifier.urihttp://hdl.handle.net/10033/610428en
dc.description.abstractSystemically applied Salmonella enterica spp. have been shown to invade and colonize neoplastic tissues where it retards the growth of many tumors. This offers the possibility to use the bacteria as a vehicle for the tumor specific delivery of therapeutic molecules. Specificity of such delivery is solely depending on promoter sequences that control the production of a target molecule. We have established the functional structure of bacterial promoters that are transcriptionally active exclusively in tumor tissues after systemic application. We observed that the specific transcriptional activation is accomplished by a combination of a weak basal promoter and a strong FNR binding site. This represents a minimal set of control elements required for such activation. In natural promoters, additional DNA remodeling elements are found that alter the level of transcription quantitatively. Inefficiency of the basal promoter ensures the absence of transcription outside tumors. As a proof of concept, we compiled an artificial promoter sequence from individual motifs representing FNR and basal promoter and showed specific activation in a tumor microenvironment. Our results open possibilities for the generation of promoters with an adjusted level of expression of target proteins in particular for applications in bacterial tumor therapy.en
dc.language.isoenen
dc.titleComposing a Tumor Specific Bacterial Promoter.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalPloS oneen

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