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Angew Chem Int Ed Engl ; 58(44): 15646-15649, 2019 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-31404473

RESUMO

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.


Assuntos
Sistemas de Liberação de Medicamentos , Edição de Genes , Células-Tronco Pluripotentes Induzidas/metabolismo , Integrases/administração & dosagem , Integrases/metabolismo , Peptídeos/química , Polímeros/química , Células HEK293 , Humanos , Estrutura Molecular , Peptídeos/farmacocinética , Polímeros/farmacocinética
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