Show simple item record

dc.contributor.authorTuranov, Anton A
dc.contributor.authorHassler, Matthew R.
dc.contributor.authorAshar-Patel, Ami
dc.contributor.authorAlterman, Julia F.
dc.contributor.authorColes, Andrew H.
dc.contributor.authorHaraszti, Reka A
dc.contributor.authorRoux, Loic
dc.contributor.authorGodinho, Bruno M D C
dc.contributor.authorEcheverria, Dimas
dc.contributor.authorKarumanchi, S. Ananth
dc.contributor.authorMoore, Melissa J.
dc.contributor.authorKhvorova, Anastasia
dc.date2022-08-11T08:08:23.000
dc.date.accessioned2022-08-23T15:53:35Z
dc.date.available2022-08-23T15:53:35Z
dc.date.issued2018-11-19
dc.date.submitted2019-03-11
dc.identifier.citation<p>Nat Biotechnol. 2018 Nov 19. pii: nbt.4297. doi: 10.1038/nbt.4297. [Epub ahead of print] <a href="https://doi.org/10.1038/nbt.4297">Link to article on publisher's site</a></p>
dc.identifier.issn1087-0156 (Linking)
dc.identifier.doi10.1038/nbt.4297
dc.identifier.pmid30451990
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29382
dc.description<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
dc.description.abstractPreeclampsia is a placentally induced hypertensive disorder of pregnancy that is associated with substantial morbidity and mortality to mothers and fetuses. Clinical manifestations of preterm preeclampsia result from excess circulating soluble vascular endothelial growth factor receptor FLT1 (sFLT1 or sVEGFR1) of placental origin. Here we identify short interfering RNAs (siRNAs) that selectively silence the three sFLT1 mRNA isoforms primarily responsible for placental overexpression of sFLT1 without reducing levels of full-length FLT1 mRNA. Full chemical stabilization in the context of hydrophobic modifications enabled productive siRNA accumulation in the placenta (up to 7% of injected dose) and reduced circulating sFLT1 in pregnant mice (up to 50%). In a baboon preeclampsia model, a single dose of siRNAs suppressed sFLT1 overexpression and clinical signs of preeclampsia. Our results demonstrate RNAi-based extrahepatic modulation of gene expression with nonformulated siRNAs in nonhuman primates and establish a path toward a new treatment paradigm for patients with preterm preeclampsia.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=30451990&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1038/nbt.4297
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.subjectBiotechnology
dc.subjectFemale Urogenital Diseases and Pregnancy Complications
dc.subjectGenetics and Genomics
dc.subjectMaternal and Child Health
dc.subjectNucleic Acids, Nucleotides, and Nucleosides
dc.subjectTherapeutics
dc.titleRNAi modulation of placental sFLT1 for the treatment of preeclampsia
dc.typeJournal Article
dc.source.journaltitleNature biotechnology
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1612
dc.identifier.contextkey13997971
html.description.abstract<p>Preeclampsia is a placentally induced hypertensive disorder of pregnancy that is associated with substantial morbidity and mortality to mothers and fetuses. Clinical manifestations of preterm preeclampsia result from excess circulating soluble vascular endothelial growth factor receptor FLT1 (sFLT1 or sVEGFR1) of placental origin. Here we identify short interfering RNAs (siRNAs) that selectively silence the three sFLT1 mRNA isoforms primarily responsible for placental overexpression of sFLT1 without reducing levels of full-length FLT1 mRNA. Full chemical stabilization in the context of hydrophobic modifications enabled productive siRNA accumulation in the placenta (up to 7% of injected dose) and reduced circulating sFLT1 in pregnant mice (up to 50%). In a baboon preeclampsia model, a single dose of siRNAs suppressed sFLT1 overexpression and clinical signs of preeclampsia. Our results demonstrate RNAi-based extrahepatic modulation of gene expression with nonformulated siRNAs in nonhuman primates and establish a path toward a new treatment paradigm for patients with preterm preeclampsia.</p>
dc.identifier.submissionpathfaculty_pubs/1612
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentRNA Therapeutics Institute


This item appears in the following Collection(s)

Show simple item record