Deadly diseases can be treated before birth through gene editing

Washington: In a first, scientists conducted prenatal gene editing to prevent a lethal metabolic disorder in animals, providing the opportunity to treat human congenital diseases before birth.

Using both the CRISPR-Cas9 and Base Editor 3 (BE3) gene editing tools, researchers from the University of Pennsylvania and the Children's Hospital of Philadelphia (CHOP) to States Have reduced cholesterol levels in healthy mice treated in utero by targeting a gene regulating these levels. .

They also used prenatal gene editing to improve liver function and prevent neonatal death in a subgroup of mice modified by a mutation causing lethal liver disease, hereditary tyrosinemia type 1 (HT1). ).

In humans, HT1 usually appears during infancy and can often be treated with the help of a drug called nitisinone and a strict diet. However, when treatments fail, patients are at risk for liver failure or liver cancer.

Prenatal treatment could pave the way for disease prevention, for HT1 and potentially for other congenital disorders.

"Our ultimate goal is to translate the approach used in these proof-of-concept studies to treat serious diseases diagnosed early in pregnancy," said William H Peranteau, pediatric and fetal surgeon at the Fetal Diagnosis and Treatment Center. of CHOP.

"We hope to expand this strategy to intervene before birth in congenital diseases that, for most patients, currently do not provide effective treatment and lead to death or serious complications in infants," Peranteau said.

"We used basic editing to suppress the effects of a genetic mutation causing disease," said Kiran Musunuru, an associate professor at the University of Pennsylvania.

"We also plan to use the same basic editing technique not only to disrupt the effects of a mutation, but also to directly correct the mutation," Musunuru said.

In this study, the scientists used the Basic Editor 3 (BE3), which uses short intermixed palindromic repeats (CRISPR), adds to a CRISPR-associated protein 9 modified to form a partially active version of the CRISPR. CRISPR-Case 9 tool, and exploits it as a guiding device to carry an enzyme to a very specific genetic location in the liver cells of fetal mice.

The enzyme chemically modified the targeted genetic sequence, changing one basic type of DNA into another.

After birth, mice in the study carried stable amounts of edited liver cells up to three months after prenatal treatment, with no evidence of unwanted unwanted assembly at other DNA sites.

"A significant amount of work needs to be done before prenatal gene editing can be transmitted to the clinic, including research on more clinically relevant delivery mechanisms and the safety of this approach," said Peranteau.

End of