Better method of CRISPR delivery to respiratory tract

Respiratory tract is easy to reach from external environment, but at the same time epithelial cells lining up the airways are hard to transfect with viruses – typical way of gene therapy delivery. Other methods, such as nanomaterials and lipids, also have low efficiency because of mucus.

New method applies cell-penetrating peptides, designed to shuttle CRISPR components into the cells. The peptides are 25-34 amino acid long and perform their function by cationic residues and highly hydrophobic residues, letting purified CRISPR-associated proteins (Cas9 and Cas12a) with guide RNA through the membrane.

Scientists achieved 27-35% efficiency of editing in epithelial cell lines and 13% efficiency of editing in airways of mice. Additionally, they showed two times better efficiency in editing human NK cells, improving it from 10% to 23-26%.

The method offers an attractive approach to cystic fibrosis, as correcting 5-15% of airway epithelial cells should restore normal levels of secretion.

Senior author of the study concludes:

We have to be able to safely deliver the materials. This research is one step in that path.

Paul B. McCray Jr.

Photo: Tom Deerinck, National Center for Microscopy and Imaging Research (NCMIR).
Publication: Krishnamurthy, S., Wohlford-Lenane, C., Kandimalla, S. et al. Engineered amphiphilic peptides enable delivery of proteins and CRISPR-associated nucleases to airway epithelia. Nat Commun 10, 4906 (2019) doi:10.1038/s41467-019-12922-y

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