Co-delivery of genes can be confounded by bicistronic vector design

Hanieh Moradian; Manfred Gossen; Andreas Lendlein

doi:10.1557/s43579-021-00128-7

Co-delivery of genes can be confounded by bicistronic vector design

MRS Commun. 2022;12(2):145-153. doi: 10.1557/s43579-021-00128-7. Epub 2022 Feb 18.

Authors

Hanieh Moradian^{1

2

3}, Manfred Gossen^{1

2}, Andreas Lendlein^{1

2

3}

Affiliations

¹ Institute of Active Polymers, Helmholtz-Zentrum Hereon, 14513 Teltow, Germany.
² Berlin-Brandenburg Center for Regenerative Therapies (BCRT), 13353 Berlin, Germany.
³ Institute of Biochemistry and Biology, University of Potsdam, 14476 Potsdam, Germany.

Abstract

Maximizing the efficiency of nanocarrier-mediated co-delivery of genes for co-expression in the same cell is critical for many applications. Strategies to maximize co-delivery of nucleic acids (NA) focused largely on carrier systems, with little attention towards payload composition itself. Here, we investigated the effects of different payload designs: co-delivery of two individual "monocistronic" NAs versus a single bicistronic NA comprising two genes separated by a 2A self-cleavage site. Unexpectedly, co-delivery via the monocistronic design resulted in a higher percentage of co-expressing cells, while predictive co-expression via the bicistronic design remained elusive. Our results will aid the application-dependent selection of the optimal methodology for co-delivery of genes.

Supplementary information: The online version contains supplementary material available at 10.1557/s43579-021-00128-7.

Keywords: Molecular; Packaging; Protein.