{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:23:41Z","timestamp":1790619821607,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Wisconsin National Primate Research Center"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P51OD11106"],"award-info":[{"award-number":["P51OD11106"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Currently, there are no placenta-targeted treatments to alter the in utero environment for administration to pregnant women who receive a diagnosis of fetal growth restriction (FGR). Water-soluble polymers have a distinguished record of clinical relevance outside of pregnancy. We have demonstrated the effective delivery of polymer-based nanoparticles containing a non-viral human insulin-like growth factor 1 (IGF1) transgene to correct placental insufficiency in small animal models of FGR. Our goals were to extend these studies to a proof-of-concept study in the pregnant macaque, establish feasibility of nanoparticle-mediated gene therapy delivery to trophoblasts, and investigate the acute maternal, placental, and fetal responses to treatment. Pregnant macaques underwent ultrasound-guided intraplacental injections of nanoparticles (GFP- or IGF1-expressing plasmid under the control of the trophoblast-specific PLAC1 promoter complexed with a HPMA\u2013DMEAMA co-polymer) at approximately gestational day 100 (term\u2009=\u2009165\u2009days). Fetectomy was performed 24\u2009h (GFP; n\u2009=\u20091), 48\u2009h (IGF1; n\u2009=\u20093) or 10\u2009days (IGF1; n\u2009=\u20093) after nanoparticle delivery. Routine pathological assessment was performed on biopsied maternal tissues and placental and fetal tissues. Maternal blood was analyzed for complete blood count (CBC), immunomodulatory proteins and growth factors, progesterone (P4), and estradiol (E2). Placental ERK\/AKT\/mTOR signaling was assessed using Western blot and qPCR. Fluorescent microscopy and in situ hybridization confirmed placental uptake and transient transgene expression in villous syncytiotrophoblast. No off-target expression was observed in either maternal or fetal tissues. Histopathological assessment of the placenta recorded observations not necessarily related to the IGF1 nanoparticle treatment. In maternal blood, CBCs, P4, and E2 remained within the normal range for pregnant macaques across the treatment period. Changes to placental ERK and AKT signaling at 48\u2009h and 10\u2009days after IGF1 nanoparticle treatment indicated an upregulation in placental homeostatic mechanisms to prevent overactivity in the normal pregnancy environment. The lack of adverse maternal reaction to nanoparticle-mediated IGF1 treatment, combined with changes in placental signaling to maintain homeostasis, indicates no deleterious impact of treatment during the acute phase of study.<\/jats:p>","DOI":"10.1093\/molehr\/gaae038","type":"journal-article","created":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T00:18:25Z","timestamp":1730506705000},"source":"Crossref","is-referenced-by-count":10,"title":["Placental gene therapy in nonhuman primates: a pilot study of maternal, placental, and fetal response to non-viral, polymeric nanoparticle delivery of\n                    <i>IGF1<\/i>"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3867-7784","authenticated-orcid":false,"given":"Rebecca L","family":"Wilson","sequence":"first","affiliation":[{"name":"Department of Physiology and Aging, College of Medicine, University of Florida , Gainesville, FL,","place":["USA"]},{"name":"Center for Research in Perinatal Outcomes, University of Florida , Gainesville, FL,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna Kropp","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison , Madison, WI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baylea N","family":"Davenport","sequence":"additional","affiliation":[{"name":"Department of Physiology and Aging, College of Medicine, University of Florida , Gainesville, FL,","place":["USA"]},{"name":"Center for Research in Perinatal Outcomes, University of Florida , Gainesville, FL,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Ren","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison , Madison, WI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan T","family":"Keding","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison , Madison, WI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A","family":"Shaw","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison , Madison, WI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele L","family":"Schotzko","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison , Madison, WI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M","family":"Antony","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Wisconsin\u2013Madison , Madison, WI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather A","family":"Simmons","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison , Madison, WI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaddeus G","family":"Golos","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison , Madison, WI,","place":["USA"]},{"name":"Department of Obstetrics and Gynecology, University of Wisconsin\u2013Madison , Madison, WI,","place":["USA"]},{"name":"Department of Comparative Biosciences, University of Wisconsin\u2013Madison , Madison, WI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7356-8420","authenticated-orcid":false,"given":"Helen 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