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

Autor: Blum AP; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.; Departments of Chemistry, Hamilton College, Clinton, NY, USA., Nelles DA; Department of Cellular and Molecular Medicine, Stem Cell Program, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA, USA., Hidalgo FJ; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA., Touve MA; Departments of Chemistry, Materials Science & Engineering, Biomedical Engineering, International Institute for Nanotechnology, Northwestern University, Evanston, IL, USA., Sim DS; Departments of Chemistry, Hamilton College, Clinton, NY, USA., Madrigal AA; Department of Cellular and Molecular Medicine, Stem Cell Program, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA, USA., Yeo GW; Department of Cellular and Molecular Medicine, Stem Cell Program, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.; Molecular Engineering Laboratory, A*STAR, Singapore, Singapore., Gianneschi NC; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.; Departments of Chemistry, Materials Science & Engineering, Biomedical Engineering, International Institute for Nanotechnology, Northwestern University, Evanston, IL, USA.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2019 Oct 28; Vol. 58 (44), pp. 15646-15649. Date of Electronic Publication: 2019 Sep 18.
DOI: 10.1002/anie.201904894
Abstrakt: 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.
(© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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