Spray Your Way Free of Cystic Fibrosis with a Gene Editing Nasal Spray

With allergy season around the corner, you might be turning to nasal sprays to relieve the symptoms. But now Marie Egan’s lab at Yale University have developed a very different type of nasal spray that helps overcome a disorder much more devastating: Cystic Fibrosis. Earlier attempts to correct the F508del CFTR mutation have been undertaken using CRISPRs in intestinal stem cell organoids and a mouse model, but now a different gene editing technology has been custom designed for effect.

The technology known as triplex-forming peptide nucliec acids (PNAs) are a DNA mimic that involve bases modified with polyamide backbones that are resistant to degradation and can target and bind sequence where it induces site specific recombination with a donor template. The triplex-forming PNAs can then be packaged into biodegradable polymers alongside some donor template to allow for in vivo delivery of an editing system that doesn’t require transforming the system in as well.

Here’s what they found:

• A genome editing efficiency of 25% in vitro and in vivo editing of the nasal epithelium at 5% and the lungs at 1%.
• Deep sequencing revealed substantially less off-target effects than in CRISPR models.
• Despite lower editing efficiency comparing in vitro (25%) to in vivo, previous CRIPSR techniques actually had lower rates in vivo and ZFNs only achieved a 1% correction rate in vitro.
• The delivery doesn’t require retroviral transformation of the CRISPR system, a previously big clinical roadblock overcome, and no one yet has tried in vivo delivery using CRISPR.

Egan shares that “The percentage of cells in humans and in mice that we were able to edit was higher than has been previously reported in gene editing technology” but notes that “…this is step one in a long process. The technology could be used as a way to fix the basic genetic defect in cystic fibrosis.”

Check out your alternative gene editing options in Nature Communications, April 2015.