CRISPR Gene Editing Technology Successfully Treated Lethal Lung Disease in Animal Models

In a proof-of-concept study recently published in Science Translational Medicine, researchers from Penn Medicine and the Children’s Hospital of Philadelphia (CHOP) were able to edit out a lethal lung disease using CRISPR in utero mice models.

“We wanted to know if this could work at all. The trick was how to direct the gene-editing machinery to target cells that line the airways of the lungs,” Edward E. Morrisey, PhD, professor of Cardiovascular Medicine and Cell and Developmental Biology in the Perelman School of Medicine at the University of Pennsylvania, said in a statement.

The study authors are hoping to solve lung conditions such as congenital disease like cystic fibrosis, surfactant protein deficiency, and alpha-1 antitrypsin.

The researchers showed that by precisely timing the in utero delivery of CRISPR gene-editing reagents to the amniotic fluid resulted in targeted changes in the lungs of mice. Specifically, researchers targeted inherited surfactant protein syndromes. In delivering the CRISPR gene-editing system to mice in utero, the team was able to deactivate the mutation responsible for surfactant protein C (SFTPC) deficiency, and more than 22% of the mice survived. If left untreated, 100% of mice die from respiratory failure hours after birth.

“The ability to cure or mitigate a disease via gene editing in mid- to late gestation before birth and the onset of irreversible pathology is very exciting. This is particularly true for diseases that affect the lungs, whose function becomes dramatically more important at the time of birth," William H. Peranteau, MD, a coauthor of the study and an investigator at CHOP’s Center for Fetal Research, said in a press release.

Using CRISPR to edit genes prior to birth has created a stir in the medical community as of late after a Chinese scientist, He Jiankui, used the technology in human embryos to produce the world’s first genome-edited babies. However, Peranteau emphasized that early embryo editing is different from mid- to late-gestation editing of a fetus, as he and the other study authors did not see evidence that germline editing had occurred in the models and explained that the editing would not be passed on to subsequent generations.

Future studies will look to increase the efficiency of gene editing in the epithelial lining of lungs, as well as evaluate different mechanisms of delivering gene editing technology to the lungs. “Different gene editing techniques are also being explored that may one day be able to correct the exact mutations observed in genetic lung diseases in infants,” said Morrisey.

Reference

Alapati D, Zacharias W, Hartman H, et al. In utero gene editing for monogenic lung disease [published online April 17, 2019]. Sci Trans Med. doi: 10.1126/scitranslmed.aav8375