ABSTRACT
This Viewpoint discusses the long-term medical, emotional, and financial implications of using amnioinfusion to treat anhydramnios; outlines the ongoing Renal Anhydramnios Fetal Therapy (RAFT) trial, which aims to document outcomes and survival in infants after amnioinfusion; and suggests that amnioinfusions be withheld in early anhydramnios, pending the findings of the RAFT trial.
Subject(s)
Amniotic Fluid , Infusions, Parenteral , Oligohydramnios , Female , Humans , Pregnancy , Delivery, Obstetric , Oligohydramnios/therapy , Infusions, Parenteral/ethics , Ethics, MedicalABSTRACT
Gene therapy targeting of kidneys has been largely unsuccessful. Recently, a recombinant adeno-associated virus (rAAV) vector was used to target adult mouse kidneys. Our hypothesis is that a pseudotyped rAAV 2/9 vector can produce fetal kidney-specific expression of the green fluorescent protein (GFP) gene following maternal tail vein injection of pregnant mice. Pregnant mice were treated with rAAV2/9 vectors with either the ubiquitous cytomegalovirus promoter or the minimal NPHS1 promoter to drive kidney-specific expression of GFP. Kidneys from dams and pups were analyzed for vector DNA, gene expression, and protein. Vector DNA was identified in kidney tissue out to 12 weeks at low but stable levels, with levels higher in dams than that in pups. Robust GFP expression was identified in the kidneys of both dams and pups treated with the cytomegalovirus (CMV)-enhanced green fluorescent protein (eGFP) vector. When treated with the NPHS1-eGFP vector, dams and pups showed expression of GFP only in kidneys, localized to the glomeruli. An 80-fold increase in GFP mRNA expression in dams and a nearly 12-fold increase in pups was found out to 12 weeks of life. Selective targeting of the fetal kidney with a gene therapy vector was achieved by utilizing the pseudotyped rAAV 2/9 vector containing the NPHS1 promoter.
