Massachusetts Chapter of the American College of Surgeons

Back to 2022 Display Posters


Transamniotic Fetal mRNA Delivery as a Novel Perinatal Therapy: Potential Applicability to Cystic Fibrosis-Associated Meconium Ileus
Kamila Moskowitzova, Ashlyn E. Whitlock, Yash Shroff, David Zurakowski, Dario O. Fauza
Department of Surgery, Boston Children’s Hospital and Harvard Medical School, Boston, MA

Background: Exogenous mRNA administration has emerged as a powerful novel strategy for the management of an assortment of conditions, including surgical diseases. We sought to determine whether the minimally invasive transamniotic route could be an alternative for fetal mRNA administration, as well as for delivery of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) mRNA to the fetal intestine, the latter as a potential strategy for the prevention of CF-associated meconium ileus.
Methods: Pregnant dams received intra-amniotic injections (50?L) in all fetuses (n=195) on gestation day 17 (E17; term E21-22) of either luciferase or human CFTR mRNA, both encapsulated by a semi-synthetic composite (lipopolyplex). Injections of lipopolyplex without mRNA served as controls. Samples from up to 14 fetal sites, depending on the group, were screened for the mRNA product via luminometry (luciferase) or ELISA (CFTR) at different time points until term.
Results: When controlled by lipopolyplex without mRNA, luciferase was detected in the animals that received encapsulated mRNA in the amniotic fluid, amnion, chorion, umbilical cord, and placenta (p=0.033 to <0.001), as well as in the fetal liver, stomach, intestines, and lungs (p=0.043 to 0.002). Human CFTR was detected in the small intestine from the mRNA group at all time points (p<0.001 for all).
Conclusion: Encapsulated exogenous mRNA can be incorporated by the fetus at select anatomical sites after simple intra-amniotic administration in a rodent model. Transamniotic fetal mRNA delivery could become a practicable novel strategy for the perinatal management of a variety of diseases, including the prevention of meconium ileus associated with cystic fibrosis.


Back to 2022 Display Posters