Peptide Brush Polymers for Efficient Delivery of a Gene Editing Protein to Stem Cells
Corresponding Author
Prof. Angela P. Blum
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA
Departments of Chemistry, Hamilton College, Clinton, NY, USA
These authors contributed equally to this work.
Search for more papers by this authorDr. David A. Nelles
Department of Cellular and Molecular Medicine, Stem Cell Program, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA, USA
These authors contributed equally to this work.
Search for more papers by this authorFrancisco J. Hidalgo
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA
Search for more papers by this authorDr. Mollie A. Touve
Departments of Chemistry, Materials Science & Engineering, Biomedical Engineering, International Institute for Nanotechnology, Northwestern University, Evanston, IL USA
Search for more papers by this authorDeborah S. Sim
Departments of Chemistry, Hamilton College, Clinton, NY, USA
Search for more papers by this authorAssael A. Madrigal
Department of Cellular and Molecular Medicine, Stem Cell Program, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA, USA
Search for more papers by this authorCorresponding Author
Prof. Gene W. Yeo
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
Search for more papers by this authorCorresponding Author
Prof. Nathan C. Gianneschi
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
Search for more papers by this authorCorresponding Author
Prof. Angela P. Blum
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA
Departments of Chemistry, Hamilton College, Clinton, NY, USA
These authors contributed equally to this work.
Search for more papers by this authorDr. David A. Nelles
Department of Cellular and Molecular Medicine, Stem Cell Program, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA, USA
These authors contributed equally to this work.
Search for more papers by this authorFrancisco J. Hidalgo
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA
Search for more papers by this authorDr. Mollie A. Touve
Departments of Chemistry, Materials Science & Engineering, Biomedical Engineering, International Institute for Nanotechnology, Northwestern University, Evanston, IL USA
Search for more papers by this authorDeborah S. Sim
Departments of Chemistry, Hamilton College, Clinton, NY, USA
Search for more papers by this authorAssael A. Madrigal
Department of Cellular and Molecular Medicine, Stem Cell Program, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA, USA
Search for more papers by this authorCorresponding Author
Prof. Gene W. Yeo
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
Search for more papers by this authorCorresponding Author
Prof. Nathan C. Gianneschi
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
Search for more papers by this authorGraphical Abstract
(B)rush delivery: The efficient delivery of an active DNA-modifying enzyme to human stem cells through high-density cell penetrating peptide brush polymers is reported. Brush polymer formulations utilizing cell penetrating peptides could promote delivery of Cre recombinase, whereas oligopeptides alone or oligopeptides displayed on nanoparticles did not.
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.
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