Transcriptional Targeting of Dendritic Cells Using an Optimized Human Fascin1 Gene Promoter

Zeyn Y, Hobernik D, Wilk U, Pöhmerer J, Hieber C, Medina-Montano C, Röhrig N, Strähle CF, Thoma-Kreß A, Wagner E, Bros M, Berger S (2023)

Publication Language: English

Publication Type: Journal article

Publication year: 2023

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 24

Article Number: 16938

Journal Issue: 23

DOI: 10.3390/ijms242316938

Abstract

Deeper knowledge about the role of the tumor microenvironment (TME) in cancer development and progression has resulted in new strategies such as gene-based cancer immunotherapy. Whereas some approaches focus on the expression of tumoricidal genes within the TME, DNA-based vaccines are intended to be expressed in antigen-presenting cells (e.g., dendritic cells, DCs) in secondary lymphoid organs, which in turn induce anti-tumor T cell responses. Besides effective delivery systems and the requirement of appropriate adjuvants, DNA vaccines themselves need to be optimized regarding efficacy and selectivity. In this work, the concept of DC-focused transcriptional targeting was tested by applying a plasmid encoding for the luciferase reporter gene under the control of a derivative of the human fascin1 gene promoter (pFscnLuc), comprising the proximal core promoter fused to the normally more distantly located DC enhancer region. DC-focused activity of this reporter construct was confirmed in cell culture in comparison to a standard reporter vector encoding for luciferase under the control of the strong ubiquitously active cytomegalovirus promoter and enhancer (pCMVLuc). Both plasmids were also compared upon intravenous administration in mice. The organ- and cell type-specific expression profile of pFscnLuc versus pCMVLuc demonstrated favorable activity especially in the spleen as a central immune organ and within the spleen in DCs.

Authors with CRIS profile

Caroline Mohr Institute of Clinical and Molecular Virology Andrea Thoma-Kreß Institute of Clinical and Molecular Virology

Involved external institutions

Universitätsmedizin der Johannes Gutenberg-Universität Mainz DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE)

How to cite

APA:

Zeyn, Y., Hobernik, D., Wilk, U., Pöhmerer, J., Hieber, C., Medina-Montano, C.,... Berger, S. (2023). Transcriptional Targeting of Dendritic Cells Using an Optimized Human Fascin1 Gene Promoter. International Journal of Molecular Sciences, 24(23). https://doi.org/10.3390/ijms242316938

MLA:

Zeyn, Yanira, et al. "Transcriptional Targeting of Dendritic Cells Using an Optimized Human Fascin1 Gene Promoter." International Journal of Molecular Sciences 24.23 (2023).

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