# Placental-specific therapy for fetal growth restriction

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2021 · $310,109

## Abstract

Project Summary
Fetal Growth Restriction (FGR) complicates 5-10% of all pregnancies in the U.S.A and currently has no
treatment. The majority of these cases are due to placental insufficiency and studies indicate that these babies
are at high risk of developing obesity, diabetes and cardiovascular disease in adulthood. The long-term goal is
to establish safe, efficacious and specific non-invasive placental gene transfer in order to establish potential
treatment strategies for fetal growth restriction. The overall objective of this application is to develop a polymer-
based nanoparticle that can be taken up by the human syncytium and result in transgene expression and allow
tracking and targeting developments for non-placental injection of the nanoparticle. The rationale behind this
proposal is that it is expected to make significant steps toward a specific delivery mechanism for therapy in the
placenta and to broaden the knowledge by which substances are endocytosed by the syncytium of the
placenta.
To accomplish the objective of this application the candidate intends to pursue the following specific aims:
Aim 1: Targeting nanoparticle delivery and transgene expression to the placental syncytiotrophoblast.
We hypothesize that peptide conjugation and the incorporation of organ-specific microRNAs will aid placental
nanoparticle uptake and reduce off-target transgene expression. We will utilize in vitro human and in vivo
murine studies to investigate nanoparticle uptake, assess transgene expression and address any off-target
effects following delivery into the maternal circulation.
Aim 2: Placental therapy in models of pre-existing fetal growth restriction. We hypothesize that
nanoparticle-mediated placental IGF-1 therapy will rectify impaired placental development and fetal growth in
animal models of pre-existing fetal growth restriction. We will use the Enos-/- mouse strain and a Guinea pig
model of maternal nutrition restriction to investigate effects of placental-specific therapy after the onset of fetal
growth restriction as would be the scenario in human pregnancy until the ability to predict placental
insufficiency is developed.
The use of placentally-targeted therapeutics are highly innovative, challenging current paradigms for the
management of fetal growth restriction and moving gene therapy beyond imaging, targeting, and destruction of
unwanted cells. The proposed research is significant because development of a placental targeting system to
allow preferential nanoparticle delivery from the maternal circulation to the syncytiotrophoblast is essential to
move this technology forward. Ultimately such capabilities and knowledge has the potential to lead to the
development of the first effective treatment for Fetal Growth Restriction.

## Key facts

- **NIH application ID:** 10237421
- **Project number:** 5R01HD090657-06
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** HELEN N JONES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $310,109
- **Award type:** 5
- **Project period:** 2017-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237421

## Citation

> US National Institutes of Health, RePORTER application 10237421, Placental-specific therapy for fetal growth restriction (5R01HD090657-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10237421. Licensed CC0.

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