Society for Maternal-Fetal Medicine Special Statement: Beyond the scalpel: in utero fetal gene therapy and curative medicine

Foetal genome editing

“…Despite the excitement surrounding modern postnatal gene editing approaches that offer the promise of a one-shot treatment to prevent progression of disease pathology, in-utero therapies offer the additional potential to prevent the onset of disease pathology altogether [3]. Indeed, the onset of prenatal disease pathology has been noted in a number of diseases, including lysosomal storage disorders such as the mucopolysaccharidoses, pulmonary diseases such as cystic fibrosis, metabolic liver diseases, including hereditary tyrosinemia type 1, and neurologic pathologies such as Gaucher disease [11,12 ▪▪ ,13,14]. In particular, for severe lung, neurologic and metabolic diseases, irreversible disease is often present by the second or third trimester, leading to devastating and potentially deadly consequences soon after birth, making these good targets for in-utero gene therapy and editing [6,13].…”

“…Indeed, the onset of prenatal disease pathology has been noted in a number of diseases, including lysosomal storage disorders such as the mucopolysaccharidoses, pulmonary diseases such as cystic fibrosis, metabolic liver diseases, including hereditary tyrosinemia type 1, and neurologic pathologies such as Gaucher disease [11,12 ▪▪ ,13,14]. In particular, for severe lung, neurologic and metabolic diseases, irreversible disease is often present by the second or third trimester, leading to devastating and potentially deadly consequences soon after birth, making these good targets for in-utero gene therapy and editing [6,13]. Importantly, recent improvements in the precision, cost and accuracy of prenatal genetic testing have increased our ability to diagnose congenital diseases in the early stages of foetal development and therefore make it increasingly feasible to treat genetic disease in the prenatal setting [12 ▪▪ ,13].…”

“…In particular, for severe lung, neurologic and metabolic diseases, irreversible disease is often present by the second or third trimester, leading to devastating and potentially deadly consequences soon after birth, making these good targets for in-utero gene therapy and editing [6,13]. Importantly, recent improvements in the precision, cost and accuracy of prenatal genetic testing have increased our ability to diagnose congenital diseases in the early stages of foetal development and therefore make it increasingly feasible to treat genetic disease in the prenatal setting [12 ▪▪ ,13]. Notably, the developmental ontogeny of the foetus is characterized by small body mass, a tolerogenic immune system, abundance and accessibility of progenitor and stem cells, and permeability of compartmental membranes such as the blood–brain barrier [14].…”