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Advances towards Cell-Specific Gene Transfection: A Small-Molecule Approach Allows Order-of-Magnitude Selectivity.

ABSTRACT: A transfection vector that can home in on tumors is reported. Whereas previous vectors that allow moderately cell selective gene transfection used larger systems, this small-molecule approach paved the way for precise structure-activity relationship optimization. For this, biotin, which mediates cell selectivity, was combined with the potent DNA-binding motif tetralysine-guanidinocarbonypyrrol via a hydrophilic linker, thus enabling SAR-based optimization. The new vector mediated biotin receptor (BR)-selective transfection of cell lines with different BR expression levels. Computer-based analyses of microscopy images revealed a preference of one order of magnitude for the BR-positive cell lines over the BR-negative controls.

SUBMITTER: Dirksmeyer T

PROVIDER: S-EPMC9401007 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Advances towards Cell-Specific Gene Transfection: A Small-Molecule Approach Allows Order-of-Magnitude Selectivity.

Dirksmeyer Thies T Stahl Paul P Vallet Cecilia C Knauer Shirley S Giese Michael M Schmuck Carsten C Hirschhäuser Christoph C

Chemistry (Weinheim an der Bergstrasse, Germany) 20220617 43

A transfection vector that can home in on tumors is reported. Whereas previous vectors that allow moderately cell selective gene transfection used larger systems, this small-molecule approach paved the way for precise structure-activity relationship optimization. For this, biotin, which mediates cell selectivity, was combined with the potent DNA-binding motif tetralysine-guanidinocarbonypyrrol via a hydrophilic linker, thus enabling SAR-based optimization. The new vector mediated biotin receptor ...[more]

PMID: 35604769

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