当前位置： SCI文献检索 > NATURE BIOTECHNOLOGY期刊下所有文献 > RNAi modulation of placental sFLT1 for the treatment of preeclampsia.

RNAi modulation of placental sFLT1 for the treatment of preeclampsia.

Abstract：

: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.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Turanov AA,Lo A,Hassler MR,Makris A,Ashar-Patel A,Alterman JF,Coles AH,Haraszti RA,Roux L,Godinho BMDC,Echeverria D,Pears S,Iliopoulos J,Shanmugalingam R,Ogle R,Zsengeller ZK,Hennessy A,Karumanchi SA,Moore MJ,Khvoro

doi

10.1038/nbt.4297

subject

Has Abstract

pub_date

2018-11-19 00:00:00

eissn

1087-0156

issn

1546-1696

pii

nbt.4297

pub_type

杂志文章

相关文献

NATURE BIOTECHNOLOGY文献大全
  • Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration.

    abstract：:Insertional mutagenesis represents a major hurdle to gene therapy and necessitates sensitive preclinical genotoxicity assays. Cdkn2a-/- mice are susceptible to a broad range of cancer-triggering genetic lesions. We exploited hematopoietic stem cells from these tumor-prone mice to assess the oncogenicity of prototypica...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt1216

    authors： Montini E,Cesana D,Schmidt M,Sanvito F,Ponzoni M,Bartholomae C,Sergi Sergi L,Benedicenti F,Ambrosi A,Di Serio C,Doglioni C,von Kalle C,Naldini L

    更新日期：2006-06-01 00:00:00

  • Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9.

    abstract：:CRISPR-Cas9-based genetic screens are a powerful new tool in biology. By simply altering the sequence of the single-guide RNA (sgRNA), one can reprogram Cas9 to target different sites in the genome with relative ease, but the on-target activity and off-target effects of individual sgRNAs can vary widely. Here, we use ...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt.3437

    authors： Doench JG,Fusi N,Sullender M,Hegde M,Vaimberg EW,Donovan KF,Smith I,Tothova Z,Wilen C,Orchard R,Virgin HW,Listgarten J,Root DE

    更新日期：2016-02-01 00:00:00

  • Continuous evolution of SpCas9 variants compatible with non-G PAMs.

    abstract：:The targeting scope of Streptococcus pyogenes Cas9 (SpCas9) and its engineered variants is largely restricted to protospacer-adjacent motif (PAM) sequences containing G bases. Here we report the evolution of three new SpCas9 variants that collectively recognize NRNH PAMs (where R is A or G and H is A, C or T) using ph...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/s41587-020-0412-8

    authors： Miller SM,Wang T,Randolph PB,Arbab M,Shen MW,Huang TP,Matuszek Z,Newby GA,Rees HA,Liu DR

    更新日期：2020-04-01 00:00:00

  • The paths around stem cell intellectual property.

    abstract：:Can new approaches for deriving human stem cells circumnavigate existing patents that dominate embryonic stem cell intellectual property? ...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt0406-411

    authors： Taymor KS,Scott CT,Greely HT

    更新日期：2006-04-01 00:00:00

  • Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes.

    abstract：:Identification of the peptides recognized by individual T cells is important for understanding and treating immune-related diseases. Current cytometry-based approaches are limited to the simultaneous screening of 10-100 distinct T-cell specificities in one sample. Here we use peptide-major histocompatibility complex (...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt.3662

    authors： Bentzen AK,Marquard AM,Lyngaa R,Saini SK,Ramskov S,Donia M,Such L,Furness AJ,McGranahan N,Rosenthal R,Straten PT,Szallasi Z,Svane IM,Swanton C,Quezada SA,Jakobsen SN,Eklund AC,Hadrup SR

    更新日期：2016-10-01 00:00:00

  • Tandem fluorescent protein timers for in vivo analysis of protein dynamics.

    abstract：:The functional state of a cell is largely determined by the spatiotemporal organization of its proteome. Technologies exist for measuring particular aspects of protein turnover and localization, but comprehensive analysis of protein dynamics across different scales is possible only by combining several methods. Here w...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt.2281

    authors： Khmelinskii A,Keller PJ,Bartosik A,Meurer M,Barry JD,Mardin BR,Kaufmann A,Trautmann S,Wachsmuth M,Pereira G,Huber W,Schiebel E,Knop M

    更新日期：2012-06-24 00:00:00

  • An efficient system for the evolution of aminoacyl-tRNA synthetase specificity.

    abstract：:A variety of strategies to incorporate unnatural amino acids into proteins have been pursued, but all have limitations with respect to technical accessibility, scalability, applicability to in vivo studies, or site specificity of amino acid incorporation. The ability to selectively introduce unnatural functional group...

    journal_title：Nature biotechnology

    pub_type：

    doi：10.1038/nbt742

    authors： Santoro SW,Wang L,Herberich B,King DS,Schultz PG

    更新日期：2002-10-01 00:00:00

  • Author Correction: Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs.

    abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title：Nature biotechnology

    pub_type： 已发布勘误

    doi：10.1038/s41587-019-0292-y

    authors： Qu L,Yi Z,Zhu S,Wang C,Cao Z,Zhou Z,Yuan P,Yu Y,Tian F,Liu Z,Bao Y,Zhao Y,Wei W

    更新日期：2019-11-01 00:00:00

  • Regeneration of transgenic cassava plants (Manihot esculenta Crantz) from microbombarded embryogenic suspension cultures.

    abstract：:A protocol was established for the introduction of DNA into embryogenic suspension-derived tissues of cassava via microparticle bombardment, for the selection of genetically transformed cells, and for the regeneration of fully transgenic plants from these cells. The plasmid DNA used for bombardment contained a gene en...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt0696-731

    authors： Schöpke C,Taylor N,Cárcamo R,Konan NK,Marmey P,Henshaw GG,Beachy RN,Fauquet C

    更新日期：1996-06-01 00:00:00

  • Publisher Correction: Federated discovery and sharing of genomic data using Beacons.

    abstract：:In the version of this article initially published, Lena Dolman's second affiliation was given as Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. The correct second affiliation is Ontario Institute for Cancer Research, Toronto, Ontario, Canada. The error has been corrected in the HTML ...

    journal_title：Nature biotechnology

    pub_type： 杂志文章,已发布勘误

    doi：10.1038/s41587-019-0094-2

    authors： Fiume M,Cupak M,Keenan S,Rambla J,de la Torre S,Dyke SOM,Brookes AJ,Carey K,Lloyd D,Goodhand P,Haeussler M,Baudis M,Stockinger H,Dolman L,Lappalainen I,Törnroos J,Linden M,Spalding JD,Ur-Rehman S,Page A,Flicek P,

    更新日期：2019-04-01 00:00:00

  • Efficient epitope mapping by bacteriophage lambda surface display.

    abstract：:A bacteriophage lambda surface expression system, lambda foo, was used for epitope mapping of human galectin-3. We constructed random epitope and peptide libraries and compared their efficiencies in the mapping. The galectin-3 cDNA was randomly digested by DNase 1 to make random epitope libraries. The libraries were s...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt0197-74

    authors： Kuwabara I,Maruyama H,Mikawa YG,Zuberi RI,Liu FT,Maruyama IN

    更新日期：1997-01-01 00:00:00

  • A mass-tolerant database search identifies a large proportion of unassigned spectra in shotgun proteomics as modified peptides.

    abstract：:Fewer than half of all tandem mass spectrometry (MS/MS) spectra acquired in shotgun proteomics experiments are typically matched to a peptide with high confidence. Here we determine the identity of unassigned peptides using an ultra-tolerant Sequest database search that allows peptide matching even with modifications ...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt.3267

    authors： Chick JM,Kolippakkam D,Nusinow DP,Zhai B,Rad R,Huttlin EL,Gygi SP

    更新日期：2015-07-01 00:00:00

  • A policy approach to the development of molecular diagnostic tests.

    abstract：:Efficiently generating evidence of clinical utility is a major challenge for ensuring clinical adoption of valuable diagnostics. A new approach to reimbursement in the United States offers a balance between evidence and incentives for molecular diagnostic tests. ...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt1110-1157

    authors： Schulman KA,Tunis SR

    更新日期：2010-11-01 00:00:00

  • A fluorescent variant of a protein from the stony coral Montipora facilitates dual-color single-laser fluorescence cross-correlation spectroscopy.

    abstract：:Dual-color fluorescence cross-correlation spectroscopy (FCCS) is a promising technique for quantifying protein-protein interactions. In this technique, two different fluorescent labels are excited and detected simultaneously within a common measurement volume. Difficulties in aligning two laser lines and emission cros...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt1207

    authors： Kogure T,Karasawa S,Araki T,Saito K,Kinjo M,Miyawaki A

    更新日期：2006-05-01 00:00:00

  • Erect leaves caused by brassinosteroid deficiency increase biomass production and grain yield in rice.

    abstract：:New cultivars with very erect leaves, which increase light capture for photosynthesis and nitrogen storage for grain filling, may have increased grain yields. Here we show that the erect leaf phenotype of a rice brassinosteroid-deficient mutant, osdwarf4-1, is associated with enhanced grain yields under conditions of ...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt1173

    authors： Sakamoto T,Morinaka Y,Ohnishi T,Sunohara H,Fujioka S,Ueguchi-Tanaka M,Mizutani M,Sakata K,Takatsuto S,Yoshida S,Tanaka H,Kitano H,Matsuoka M

    更新日期：2006-01-01 00:00:00

  • Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle.

    abstract：:Reengineering the receptor footprints of adeno-associated virus (AAV) isolates may yield variants with improved properties for clinical applications. We generated a panel of synthetic AAV2 vectors by replacing a hexapeptide sequence in a previously identified heparan sulfate receptor footprint with corresponding resid...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt.1599

    authors： Asokan A,Conway JC,Phillips JL,Li C,Hegge J,Sinnott R,Yadav S,DiPrimio N,Nam HJ,Agbandje-McKenna M,McPhee S,Wolff J,Samulski RJ

    更新日期：2010-01-01 00:00:00

  • Antibacterial discovery in actinomycetes strains with mutations in RNA polymerase or ribosomal protein S12.

    abstract：:We show that selection of drug-resistant bacterial mutants allows the discovery of antibacterial compounds. Mutant strains of a soil-isolated Streptomyces species that does not produce antibacterials synthesize a previously unknown class of antibacterial, which we name piperidamycin. Overall, 6% of non-Streptomyces ac...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt.1538

    authors： Hosaka T,Ohnishi-Kameyama M,Muramatsu H,Murakami K,Tsurumi Y,Kodani S,Yoshida M,Fujie A,Ochi K

    更新日期：2009-05-01 00:00:00

  • Insights into US public biotech sector using patenting trends.

    abstract：:Analyzing patent data from 1995-2005 show the increasing importance of patenting by small and medium-sized biotech companies. ...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt0606-643

    authors： Aggarwal S,Gupta V,Bagchi-Sen S

    更新日期：2006-06-01 00:00:00

  • A community computational challenge to predict the activity of pairs of compounds.

    abstract：:Recent therapeutic successes have renewed interest in drug combinations, but experimental screening approaches are costly and often identify only small numbers of synergistic combinations. The DREAM consortium launched an open challenge to foster the development of in silico methods to computationally rank 91 compound...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt.3052

    authors： Bansal M,Yang J,Karan C,Menden MP,Costello JC,Tang H,Xiao G,Li Y,Allen J,Zhong R,Chen B,Kim M,Wang T,Heiser LM,Realubit R,Mattioli M,Alvarez MJ,Shen Y,NCI-DREAM Community.,Gallahan D,Singer D,Saez-Rodriguez J,

    更新日期：2014-12-01 00:00:00

  • RNA interference against viruses: strike and counterstrike.

    abstract：:RNA interference (RNAi) is a conserved sequence-specific, gene-silencing mechanism that is induced by double-stranded RNA. RNAi holds great promise as a novel nucleic acid-based therapeutic against a wide variety of diseases, including cancer, infectious diseases and genetic disorders. Antiviral RNAi strategies have r...

    journal_title：Nature biotechnology

    pub_type： 杂志文章,评审

    doi：10.1038/nbt1369

    authors： Haasnoot J,Westerhout EM,Berkhout B

    更新日期：2007-12-01 00:00:00

  • Wavelength-shifting molecular beacons.

    abstract：:We describe wavelength-shifting molecular beacons, which are nucleic acid hybridization probes that fluoresce in a variety of different colors, yet are excited by a common monochromatic light source. The twin functions of absorption of energy from the excitation light and emission of that energy in the form of fluores...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/81192

    authors： Tyagi S,Marras SA,Kramer FR

    更新日期：2000-11-01 00:00:00

  • Targeted sequencing by proximity ligation for comprehensive variant detection and local haplotyping.

    abstract：:Despite developments in targeted gene sequencing and whole-genome analysis techniques, the robust detection of all genetic variation, including structural variants, in and around genes of interest and in an allele-specific manner remains a challenge. Here we present targeted locus amplification (TLA), a strategy to se...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt.2959

    authors： de Vree PJ,de Wit E,Yilmaz M,van de Heijning M,Klous P,Verstegen MJ,Wan Y,Teunissen H,Krijger PH,Geeven G,Eijk PP,Sie D,Ylstra B,Hulsman LO,van Dooren MF,van Zutven LJ,van den Ouweland A,Verbeek S,van Dijk KW,Cornel

    更新日期：2014-10-01 00:00:00

  • The chemical evolution of oligonucleotide therapies of clinical utility.

    abstract：:After nearly 40 years of development, oligonucleotide therapeutics are nearing meaningful clinical productivity. One of the key advantages of oligonucleotide drugs is that their delivery and potency are derived primarily from the chemical structure of the oligonucleotide whereas their target is defined by the base seq...

    journal_title：Nature biotechnology

    pub_type： 杂志文章,评审

    doi：10.1038/nbt.3765

    authors： Khvorova A,Watts JK

    更新日期：2017-03-01 00:00:00

  • Canola engineered with a microalgal polyketide synthase-like system produces oil enriched in docosahexaenoic acid.

    abstract：:Dietary omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), docosahexaenoic acid (DHA, C22:6) and eicosapentaenoic acid (EPA, C20:5) are usually derived from marine fish. Although production of both EPA and DHA has been engineered into land plants, including Arabidopsis, Camelina sativa and Brassica juncea, nei...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt.3585

    authors： Walsh TA,Bevan SA,Gachotte DJ,Larsen CM,Moskal WA,Merlo PA,Sidorenko LV,Hampton RE,Stoltz V,Pareddy D,Anthony GI,Bhaskar PB,Marri PR,Clark LM,Chen W,Adu-Peasah PS,Wensing ST,Zirkle R,Metz JG

    更新日期：2016-08-01 00:00:00

  • Turnover-based in vitro selection and evolution of biocatalysts from a fully synthetic antibody library.

    abstract：:This report describes the selection of highly efficient antibody catalysts by combining chemical selection from a synthetic library with directed in vitro protein evolution. Evolution started from a naive antibody library displayed on phage made from fully synthetic, antibody-encoding genes (the Human Combinatorial An...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt828

    authors： Cesaro-Tadic S,Lagos D,Honegger A,Rickard JH,Partridge LJ,Blackburn GM,Plückthun A

    更新日期：2003-06-01 00:00:00

  • Rapid identification of DNA-binding proteins by mass spectrometry.

    abstract：:We report a protocol for the rapid identification of DNA-binding proteins. Immobilized DNA probes harboring a specific sequence motif are incubated with cell or nuclear extract. Proteins are analyzed directly off the solid support by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The det...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/12873

    authors： Nordhoff E,Krogsdam AM,Jorgensen HF,Kallipolitis BH,Clark BF,Roepstorff P,Kristiansen K

    更新日期：1999-09-01 00:00:00

  • Generation of Rhizobium strains with improved symbiotic properties by random DNA amplification (RDA)

    abstract：:To select for bacterial strains with enhanced phenotypes, random fragments of a whole genome, or a defined region of the genome, are cloned in a nonreplicating vector. The resulting plasmids are integrated by recombination into the homologous DNA region of the original strain. Integration gives rise to a nontandem dir...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt0697-564

    authors： Mavingui P,Flores M,Romero D,Martínez-Romero E,Palacios R

    更新日期：1997-06-01 00:00:00

  • Systems strategies for developing industrial microbial strains.

    abstract：:Industrial strain development requires system-wide engineering and optimization of cellular metabolism while considering industrially relevant fermentation and recovery processes. It can be conceptualized as several strategies, which may be implemented in an iterative fashion and in different orders. The key challenge...

    journal_title：Nature biotechnology

    pub_type： 杂志文章,评审

    doi：10.1038/nbt.3365

    authors： Lee SY,Kim HU

    更新日期：2015-10-01 00:00:00

  • Author Correction: Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells.

    abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title：Nature biotechnology

    pub_type： 杂志文章,已发布勘误

    doi：10.1038/s41587-020-0427-1

    authors： Ramsköld D,Luo S,Wang YC,Li R,Deng Q,Faridani OR,Daniels GA,Khrebtukova I,Loring JF,Laurent LC,Schroth GP,Sandberg R

    更新日期：2020-03-01 00:00:00

  • Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown.

    abstract：:A central hurdle in developing small interfering RNAs (siRNAs) as therapeutics is the inefficiency of their delivery across the plasma and endosomal membranes to the cytosol, where they interact with the RNA interference machinery. With the aim of improving endosomal release, a poorly understood and inefficient proces...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt.3298

    authors： Wittrup A,Ai A,Liu X,Hamar P,Trifonova R,Charisse K,Manoharan M,Kirchhausen T,Lieberman J

    更新日期：2015-08-01 00:00:00