Peptide Brush Polymers for Efficient Delivery of a Gene Editing Protein to Stem Cells

Angela P. Blum*, David A. Nelles, Francisco J. Hidalgo, Mollie A. Touve, Deborah S. Sim, Assael A. Madrigal, Gene W. Yeo, Nathan C. Gianneschi

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The scarcity of effective means to deliver functional proteins to living cells is a central problem in biotechnology and medicine. Herein, we report the efficient delivery of an active DNA-modifying enzyme to human stem cells through high-density cell penetrating peptide brush polymers. Cre recombinase is mixed with a fluorophore-tagged polymer carrier and then applied directly to induced pluripotent stem cells or HEK293T cells. This results in efficient delivery of Cre protein as measured by activation of a genomically integrated Cre-mediated recombination reporter. We observed that brush polymer formulations utilizing cell penetrating peptides promoted Cre delivery but oligopeptides alone or oligopeptides displayed on nanoparticles did not. Overall, we report the efficient delivery of a genome-modifying enzyme to stem cells that may be generalizable to other, difficult-to-transduce cell types.

Original languageEnglish (US)
Pages (from-to)15646-15649
Number of pages4
JournalAngewandte Chemie - International Edition
Volume58
Issue number44
DOIs
StatePublished - Oct 28 2019

Keywords

  • cell penetrating peptides
  • cellular uptake
  • enzyme delivery
  • protein delivery
  • stem cells

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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    Blum, A. P., Nelles, D. A., Hidalgo, F. J., Touve, M. A., Sim, D. S., Madrigal, A. A., Yeo, G. W., & Gianneschi, N. C. (2019). Peptide Brush Polymers for Efficient Delivery of a Gene Editing Protein to Stem Cells. Angewandte Chemie - International Edition, 58(44), 15646-15649. https://doi.org/10.1002/anie.201904894