The durable cure for cystic fibrosis might start in the womb

Good news!

"... Using in utero gene editing, the researchers developed a method to deliver corrective genetic material to the fetus of mice with CF via tiny particles called nanoparticles. ...

Cystic fibrosis arises from mutations in the CF transmembrane conductance regulator, or CFTR. Because the disease is caused by a single mutation, researchers saw it as a great candidate for gene editing, specifically in utero gene editing.  ...

In the study, researchers used synthetic molecules similar to DNA — called peptide nucleic acids, or PNAs — to correct CFTR. PNA can be tweaked to bind to a particular gene containing a mutation in a strand of DNA, which can cause a lesion that the cell then removes itself. The gene is then corrected when a strand of DNA without the mutation takes its place. ...

The researchers delivered the PNA to the fetuses of mice using tiny synthetic particles called nanoparticles, which are the same size as viruses to correct the CFTR mutation before the mice were born. ..."

From the significance and abstract:

"Significance

Cystic fibrosis (CF), a monogenic disease resulting from mutations in the CF transmembrane conductance regulator (CFTR) gene, affects multiple organs, including the respiratory, gastrointestinal, and reproductive systems.

Irreversible pathology in these tissues is often already present at birth, suggesting that a true curative therapy would require intervention during fetal development.

Here, we demonstrate CFTR gene correction in multiple tissues affected by CF after a single in utero administration of nanoparticles containing gene editing cargo. We found that gene correction was durable into adulthood in mice, which resulted in functional CFTR activity in both the respiratory and gastrointestinal systems. Our work establishes the possibility that CF could be treated, or possibly cured, by a single in utero gene editing treatment.

Abstract

In utero gene editing has the potential to modify disease-causing genes in multiple developing tissues before birth, possibly allowing for normal organ development, disease improvement, and conceivably, cure. 

In cystic fibrosis (CF), a disease that arises from mutations in the CF transmembrane conductance regulator (CFTR) gene, there are signs of multiorgan disease affecting the function of the respiratory, gastrointestinal, and reproductive systems already present at birth. 

Thus, treating CF patients early is crucial for preventing or delaying irreversible organ damage. Here, we demonstrate proof-of-concept of multiorgan mutation correction in CF using peptide nucleic acids encapsulated in polymeric nanoparticles and delivered systemically in utero.

In utero editing was associated with sustained postnatal CFTR activity, at a level similar to that of wild-type mice, in both respiratory and gastrointestinal tissues, without detection of off-target mutations in partially homologous loci. This work suggests that systemic in utero gene editing represents a viable strategy for treating monogenic diseases before birth that impact multiple tissue types."

The cure for cystic fibrosis might start in the womb | Yale News "In a new study, Yale researchers develop a method that has the potential to cure cystic fibrosis prior to birth."

Systemic in utero gene editing as a treatment for cystic fibrosis (no public access)

Marie Egan, a senior author of the study