COMPOSITIONS AND METHODS FOR IN UTERO GENE EDITING FOR MONOGENIC LUNG DISEASE

摘要

Compositions and methods for in utero gene editing in mammalian lung cells are disclosed. Specifically, the disclosure provides a CRISPR-Cas system-mediated genome editing method comprising introducing into a eukaryotic cell containing and expressing a DNA molecule having a target sequence and encoding at least one mutated gene product in the lung, an engineered, non-naturally occurring CRISPR-Cas system comprising one or more vectors comprising: a) a first regulatory element operable in a eukaryotic cell operably linked to at least one nucleotide sequence encoding a CRISPR-Cas system guide RNA that hybridizes with the target sequence, and b) a second regulatory element operable in a eukaryotic cell operably linked to a nucleotide sequence encoding a Cas9 protein or variant thereof, said guide strand targets a gene in fetal or post-natal lung causing genome editing to remove one or more undesired mutations for treating monogenic diseases in prenatal or postnatal lungs.