4.6 Article

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

Journal

CHEMISTRY-A EUROPEAN JOURNAL
Volume 28, Issue 43, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202104618

Keywords

biotin; cancer cell targeting; cell-penetrating peptides; gene technology; small molecules

Funding

  1. Evonik Industries AG
  2. DFG
  3. Projekt DEAL

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This study reported a transfection vector that can home in on tumors by combining biotin, which mediates cell selectivity, with a DNA-binding motif via a hydrophilic linker. It showed a preference for the BR-positive cell lines over the BR-negative controls.
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.

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