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Engineered amphiphilic peptides enable delivery of proteins and CRISPR-associated nucleases to airway epithelia

Author

Listed:
  • Sateesh Krishnamurthy

    (University of Iowa)

  • Christine Wohlford-Lenane

    (University of Iowa)

  • Suhas Kandimalla

    (University of Iowa)

  • Gilles Sartre

    (University of Iowa)

  • David K. Meyerholz

    (University of Iowa)

  • Vanessa Théberge

    (Feldan Therapeutics, Québec)

  • Stéphanie Hallée

    (Feldan Therapeutics, Québec)

  • Anne-Marie Duperré

    (Feldan Therapeutics, Québec)

  • Thomas Del’Guidice

    (Feldan Therapeutics, Québec)

  • Jean-Pascal Lepetit-Stoffaes

    (Feldan Therapeutics, Québec)

  • Xavier Barbeau

    (Feldan Therapeutics, Québec)

  • David Guay

    (Feldan Therapeutics, Québec)

  • Paul B. McCray

    (University of Iowa)

Abstract

The delivery of biologic cargoes to airway epithelial cells is challenging due to the formidable barriers imposed by its specialized and differentiated cells. Among cargoes, recombinant proteins offer therapeutic promise but the lack of effective delivery methods limits their development. Here, we achieve protein and SpCas9 or AsCas12a ribonucleoprotein (RNP) delivery to cultured human well-differentiated airway epithelial cells and mouse lungs with engineered amphiphilic peptides. These shuttle peptides, non-covalently combined with GFP protein or CRISPR-associated nuclease (Cas) RNP, allow rapid entry into cultured human ciliated and non-ciliated epithelial cells and mouse airway epithelia. Instillation of shuttle peptides combined with SpCas9 or AsCas12a RNP achieves editing of loxP sites in airway epithelia of ROSAmT/mG mice. We observe no evidence of short-term toxicity with a widespread distribution restricted to the respiratory tract. This peptide-based technology advances potential therapeutic avenues for protein and Cas RNP delivery to refractory airway epithelial cells.

Suggested Citation

  • Sateesh Krishnamurthy & Christine Wohlford-Lenane & Suhas Kandimalla & Gilles Sartre & David K. Meyerholz & Vanessa Théberge & Stéphanie Hallée & Anne-Marie Duperré & Thomas Del’Guidice & Jean-Pascal , 2019. "Engineered amphiphilic peptides enable delivery of proteins and CRISPR-associated nucleases to airway epithelia," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12922-y
    DOI: 10.1038/s41467-019-12922-y
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    Cited by:

    1. Katarina Kulhankova & Soumba Traore & Xue Cheng & Hadrien Benk-Fortin & Stéphanie Hallée & Mario Harvey & Joannie Roberge & Frédéric Couture & Sajeev Kohli & Thomas J. Gross & David K. Meyerholz & Gar, 2023. "Shuttle peptide delivers base editor RNPs to rhesus monkey airway epithelial cells in vivo," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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