alpha-1 antitrypsin. Such fatal diseases can lead to immediate death after
birth due to respiratory failure with very few available therapeutic options.
Using CRISPR gene editing
researchers at the Children's Hospital of Philadelphia (CHOP) have edited out
the harmful mutations in animal models.
The lung is a suitable
organ for targeted delivery to correct mutated genes.
study co-leader, Professor Edward E. Morrisey of cardiovascular medicine at the
Perelman School of Medicine, UPenn; the researchers were hoping to direct the
gene-editing vehicles to target the cells lining the airways of lungs. William
H. Peranteau, MD, study co-leader and pediatric and fetal surgeon at CHOP said
that developing fetuses have some innate properties which make in-utero
gene editing quite feasible.
The research team
conducted two rounds of experiments in mouse models. In the first round, they
introduced CRISPR gene editing reagents into the amniotic fluid to target fetal
lungs. The gene editing mechanisms were introduced into the developing fetus
four days before birth which is equivalent to the human third trimester. The
small size of the fetus and the immunological status makes it easier for gene
as the amount of viral vector will be much less and the fetus will
not be in a position to mount an immunological response to bacterial Cas9
In the second
experiment, the research
team used gene editing to reduce the severity of congenital
interstitial lung disease which is caused by a deficiency in surfactant protein
C (SFTPC). Usually, all the mice born with this disease die of respiratory failure
within a few hours of birth. However, the mice treated with prenatal gene-editing
which inactivated the mutant SFTPC gene; showed an improvement in lung function
and survival. Nearly 22 percent of the mice survived after this gene-editing
The team is hoping to
move forward with further studies to evaluate better efficacy and efficiency of
gene editing in the epithelial lining of lungs and to improve gene editing
Morrisey said that the team hopes to deliver diverse gene editing technologies to
correct the exact mutations in genetic lung diseases in infants.
- In utero gene editing for monogenic lung disease - (https://stm.sciencemag.org/content/11/488/eaav8375)