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Peptide Brush Polymers for Efficient Delivery of a Gene Editing Protein to Stem Cells
Author(s) -
Blum Angela P.,
Nelles David A.,
Hidalgo Francisco J.,
Touve Mollie A.,
Sim Deborah S.,
Madrigal Assael A.,
Yeo Gene W.,
Gianneschi Nathan C.
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201904894
Subject(s) - gene delivery , stem cell , cell penetrating peptide , hek 293 cells , induced pluripotent stem cell , reporter gene , recombinase , chemistry , microbiology and biotechnology , endosome , oligopeptide , peptide , cell , gene , biology , computational biology , biochemistry , transfection , embryonic stem cell , gene expression , recombination
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.