Magnetically guided non-invasive CRISPR-Cas9/gRNA delivery across blood-brain barrier to eradicate latent HIV-1 infection View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Ajeet Kaushik, Adriana Yndart, Venkata Atluri, Sneham Tiwari, Asahi Tomitaka, Purnima Gupta, Rahul Dev Jayant, David Alvarez-Carbonell, Kamel Khalili, Madhavan Nair

ABSTRACT

CRISPR-Cas9/gRNA exhibits therapeutic efficacy against latent human immunodeficiency virus (HIV) genome but the delivery of this therapeutic cargo to the brain remains as a challenge. In this research, for the first time, we demonstrated magnetically guided non-invasive delivery of a nano-formulation (NF), composed of Cas9/gRNA bound with magneto-electric nanoparticles (MENPs), across the blood-brain barrier (BBB) to inhibit latent HIV-1 infection in microglial (hμglia)/HIV (HC69) cells. An optimized ac-magnetic field of 60 Oe was applied on NF to release Cas9/gRNA from MENPs surface and to facilitate NF cell uptake resulting in intracellular release and inhibition of HIV. The outcomes suggested that developed NF reduced HIV-LTR expression significantly in comparison to unbound Cas9/gRNA in HIV latent hμglia/HIV (HC69) cells. These findings were also validated qualitatively using fluorescence microscopy to assess NF efficacy against latent HIV in the microglia cells. We believe that CNS delivery of NF (CRISPR/Cas9-gRNA-MENPs) across the BBB certainly will have clinical utility as future personalized nanomedicine to manage neuroHIV/AIDS. More... »

PAGES

3928

References to SciGraph publications

  • 2014-11. Local Raman spectroscopy of DNA in BULLETIN OF THE LEBEDEV PHYSICS INSTITUTE
  • 2017-12. Toll-like receptor 3 activation selectively reverses HIV latency in microglial cells in RETROVIROLOGY
  • 2016-07. Magnetically guided central nervous system delivery and toxicity evaluation of magneto-electric nanocarriers in SCIENTIFIC REPORTS
  • 2015-12. CRISPR/gRNA-directed synergistic activation mediator (SAM) induces specific, persistent and robust reactivation of the HIV-1 latent reservoirs in SCIENTIFIC REPORTS
  • 2013-12. Externally controlled on-demand release of anti-HIV drug using magneto-electric nanoparticles as carriers in NATURE COMMUNICATIONS
  • 2012-08. Towards an HIV cure: a global scientific strategy in NATURE REVIEWS IMMUNOLOGY
  • 2015-12. Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells in NATURE COMMUNICATIONS
  • 2012-11. Nanotechnology: Carrying drugs in NATURE
  • 2015-07. Application of CRISPR/Cas9 genome editing to the study and treatment of disease in ARCHIVES OF TOXICOLOGY
  • 2013-12. Magneto-electric Nanoparticles to Enable Field-controlled High-Specificity Drug Delivery to Eradicate Ovarian Cancer Cells in SCIENTIFIC REPORTS
  • 2015-06. Genome editing strategies: potential tools for eradicating HIV-1/AIDS in JOURNAL OF NEUROVIROLOGY
  • 2016-04. Elimination of HIV-1 Genomes from Human T-lymphoid Cells by CRISPR/Cas9 Gene Editing in SCIENTIFIC REPORTS
  • 2018-07. Nanoparticle delivery of CRISPR into the brain rescues a mouse model of fragile X syndrome from exaggerated repetitive behaviours in NATURE BIOMEDICAL ENGINEERING
  • 2017-12. Investigation of ac-magnetic field stimulated nanoelectroporation of magneto-electric nano-drug-carrier inside CNS cells in SCIENTIFIC REPORTS
  • 2017. Advances in Personalized Nanotherapeutics in NONE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-019-40222-4

    DOI

    http://dx.doi.org/10.1038/s41598-019-40222-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112641499

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30850620


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1108", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical Microbiology", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Florida International University", 
              "id": "https://www.grid.ac/institutes/grid.65456.34", 
              "name": [
                "Department of Immunology and Nano-Medicine, Center for Personalized Nanomedicine, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kaushik", 
            "givenName": "Ajeet", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Florida International University", 
              "id": "https://www.grid.ac/institutes/grid.65456.34", 
              "name": [
                "Department of Immunology and Nano-Medicine, Center for Personalized Nanomedicine, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Yndart", 
            "givenName": "Adriana", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Florida International University", 
              "id": "https://www.grid.ac/institutes/grid.65456.34", 
              "name": [
                "Department of Immunology and Nano-Medicine, Center for Personalized Nanomedicine, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Atluri", 
            "givenName": "Venkata", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Florida International University", 
              "id": "https://www.grid.ac/institutes/grid.65456.34", 
              "name": [
                "Department of Immunology and Nano-Medicine, Center for Personalized Nanomedicine, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Tiwari", 
            "givenName": "Sneham", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Florida International University", 
              "id": "https://www.grid.ac/institutes/grid.65456.34", 
              "name": [
                "Department of Immunology and Nano-Medicine, Center for Personalized Nanomedicine, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Tomitaka", 
            "givenName": "Asahi", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Florida International University", 
              "id": "https://www.grid.ac/institutes/grid.65456.34", 
              "name": [
                "Department of Immunology and Nano-Medicine, Center for Personalized Nanomedicine, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gupta", 
            "givenName": "Purnima", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Florida International University", 
              "id": "https://www.grid.ac/institutes/grid.65456.34", 
              "name": [
                "Department of Immunology and Nano-Medicine, Center for Personalized Nanomedicine, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Jayant", 
            "givenName": "Rahul Dev", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Case Western Reserve University", 
              "id": "https://www.grid.ac/institutes/grid.67105.35", 
              "name": [
                "Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Alvarez-Carbonell", 
            "givenName": "David", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Temple University", 
              "id": "https://www.grid.ac/institutes/grid.264727.2", 
              "name": [
                "Department of Neuroscience, Lewis Katz School of Medicine, Temple University, 19140, Philadelphia, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Khalili", 
            "givenName": "Kamel", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Florida International University", 
              "id": "https://www.grid.ac/institutes/grid.65456.34", 
              "name": [
                "Department of Immunology and Nano-Medicine, Center for Personalized Nanomedicine, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Nair", 
            "givenName": "Madhavan", 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "https://doi.org/10.1146/annurev.biophys.28.1.1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000201024"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.drudis.2006.10.013", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000537417"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.jmmm.2003.12.582", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002735411"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1136/jmedgenet-2014-102968", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002742739"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/srep25309", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004272211", 
              "https://doi.org/10.1038/srep25309"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/srep16277", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009214649", 
              "https://doi.org/10.1038/srep16277"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/rmv.1778", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010211473"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/491s58a", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013453076", 
              "https://doi.org/10.1038/491s58a"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/jrs.4206", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013491258"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/srep22555", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015116002", 
              "https://doi.org/10.1038/srep22555"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1517/17425247.2014.933803", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016798463"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms2717", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018990270", 
              "https://doi.org/10.1038/ncomms2717"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s13365-014-0308-9", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020589574", 
              "https://doi.org/10.1007/s13365-014-0308-9"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.1232033", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022072971"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00204-015-1504-y", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022702690", 
              "https://doi.org/10.1007/s00204-015-1504-y"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1038/sj.jcbfm.9600330", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023706990"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1038/sj.jcbfm.9600330", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023706990"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.3103/s1068335614110025", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024854025", 
              "https://doi.org/10.3103/s1068335614110025"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.addr.2016.02.008", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028234926"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2147/ijn.s76517", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028859536"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/ange.201506030", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029765980"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/hmg/ddu125", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037875677"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/srep02953", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038036933", 
              "https://doi.org/10.1038/srep02953"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0002-9440(10)65476-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038768256"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.addr.2013.09.006", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039688958"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.tips.2009.08.004", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041486814"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nri3262", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046155496", 
              "https://doi.org/10.1038/nri3262"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.1405186111", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049574595"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/bip.20998", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050679483"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms7413", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053069309", 
              "https://doi.org/10.1038/ncomms7413"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/acschemneuro.5b00156", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053919861"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/ja800023j", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1055857687"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/ja800023j", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1055857687"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1079087771", 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12977-017-0335-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1083687350", 
              "https://doi.org/10.1186/s12977-017-0335-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12977-017-0335-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1083687350", 
              "https://doi.org/10.1186/s12977-017-0335-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/srep45663", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1084511398", 
              "https://doi.org/10.1038/srep45663"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.drudis.2017.11.010", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1092728338"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/978-3-319-63633-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1099637105", 
              "https://doi.org/10.1007/978-3-319-63633-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2217/nnm-2018-0005", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1101241104"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41551-018-0252-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1105103369", 
              "https://doi.org/10.1038/s41551-018-0252-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41551-018-0252-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1105103369", 
              "https://doi.org/10.1038/s41551-018-0252-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.3390/jnt1010001", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1105950660"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1039/9781788010481", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1109459087"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2019-12", 
        "datePublishedReg": "2019-12-01", 
        "description": "CRISPR-Cas9/gRNA exhibits therapeutic efficacy against latent human immunodeficiency virus (HIV) genome but the delivery of this therapeutic cargo to the brain remains as a challenge. In this research, for the first time, we demonstrated magnetically guided non-invasive delivery of a nano-formulation (NF), composed of Cas9/gRNA bound with magneto-electric nanoparticles (MENPs), across the blood-brain barrier (BBB) to inhibit latent HIV-1 infection in microglial (h\u03bcglia)/HIV (HC69) cells. An optimized ac-magnetic field of 60\u2009Oe was applied on NF to release Cas9/gRNA from MENPs surface and to facilitate NF cell uptake resulting in intracellular release and inhibition of HIV. The outcomes suggested that developed NF reduced HIV-LTR expression significantly in comparison to unbound Cas9/gRNA in HIV latent h\u03bcglia/HIV (HC69) cells. These findings were also validated qualitatively using fluorescence microscopy to assess NF efficacy against latent HIV in the microglia cells. We believe that CNS delivery of NF (CRISPR/Cas9-gRNA-MENPs) across the BBB certainly will have clinical utility as future personalized nanomedicine to manage neuroHIV/AIDS.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/s41598-019-40222-4", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.4455491", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2486790", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2487317", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.3535138", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.5504524", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2616178", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1045337", 
            "issn": [
              "2045-2322"
            ], 
            "name": "Scientific Reports", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "9"
          }
        ], 
        "name": "Magnetically guided non-invasive CRISPR-Cas9/gRNA delivery across blood-brain barrier to eradicate latent HIV-1 infection", 
        "pagination": "3928", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "bd9b787c018cb55e60a0b8f6a67390f29cfd8501f68cf4ea3fb6539368fd130e"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "30850620"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "101563288"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41598-019-40222-4"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1112641499"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41598-019-40222-4", 
          "https://app.dimensions.ai/details/publication/pub.1112641499"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T13:21", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000368_0000000368/records_78972_00000001.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://www.nature.com/articles/s41598-019-40222-4"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-40222-4'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-40222-4'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-40222-4'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-40222-4'


     

    This table displays all metadata directly associated to this object as RDF triples.

    273 TRIPLES      21 PREDICATES      69 URIs      21 LITERALS      9 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41598-019-40222-4 schema:about anzsrc-for:11
    2 anzsrc-for:1108
    3 schema:author Nec80d968be244d7a9e52008cff3daf1f
    4 schema:citation sg:pub.10.1007/978-3-319-63633-7
    5 sg:pub.10.1007/s00204-015-1504-y
    6 sg:pub.10.1007/s13365-014-0308-9
    7 sg:pub.10.1038/491s58a
    8 sg:pub.10.1038/ncomms2717
    9 sg:pub.10.1038/ncomms7413
    10 sg:pub.10.1038/nri3262
    11 sg:pub.10.1038/s41551-018-0252-8
    12 sg:pub.10.1038/srep02953
    13 sg:pub.10.1038/srep16277
    14 sg:pub.10.1038/srep22555
    15 sg:pub.10.1038/srep25309
    16 sg:pub.10.1038/srep45663
    17 sg:pub.10.1186/s12977-017-0335-8
    18 sg:pub.10.3103/s1068335614110025
    19 https://app.dimensions.ai/details/publication/pub.1079087771
    20 https://doi.org/10.1002/ange.201506030
    21 https://doi.org/10.1002/bip.20998
    22 https://doi.org/10.1002/jrs.4206
    23 https://doi.org/10.1002/rmv.1778
    24 https://doi.org/10.1016/j.addr.2013.09.006
    25 https://doi.org/10.1016/j.addr.2016.02.008
    26 https://doi.org/10.1016/j.drudis.2006.10.013
    27 https://doi.org/10.1016/j.drudis.2017.11.010
    28 https://doi.org/10.1016/j.jmmm.2003.12.582
    29 https://doi.org/10.1016/j.tips.2009.08.004
    30 https://doi.org/10.1016/s0002-9440(10)65476-4
    31 https://doi.org/10.1021/acschemneuro.5b00156
    32 https://doi.org/10.1021/ja800023j
    33 https://doi.org/10.1038/sj.jcbfm.9600330
    34 https://doi.org/10.1039/9781788010481
    35 https://doi.org/10.1073/pnas.1405186111
    36 https://doi.org/10.1093/hmg/ddu125
    37 https://doi.org/10.1126/science.1232033
    38 https://doi.org/10.1136/jmedgenet-2014-102968
    39 https://doi.org/10.1146/annurev.biophys.28.1.1
    40 https://doi.org/10.1517/17425247.2014.933803
    41 https://doi.org/10.2147/ijn.s76517
    42 https://doi.org/10.2217/nnm-2018-0005
    43 https://doi.org/10.3390/jnt1010001
    44 schema:datePublished 2019-12
    45 schema:datePublishedReg 2019-12-01
    46 schema:description CRISPR-Cas9/gRNA exhibits therapeutic efficacy against latent human immunodeficiency virus (HIV) genome but the delivery of this therapeutic cargo to the brain remains as a challenge. In this research, for the first time, we demonstrated magnetically guided non-invasive delivery of a nano-formulation (NF), composed of Cas9/gRNA bound with magneto-electric nanoparticles (MENPs), across the blood-brain barrier (BBB) to inhibit latent HIV-1 infection in microglial (hμglia)/HIV (HC69) cells. An optimized ac-magnetic field of 60 Oe was applied on NF to release Cas9/gRNA from MENPs surface and to facilitate NF cell uptake resulting in intracellular release and inhibition of HIV. The outcomes suggested that developed NF reduced HIV-LTR expression significantly in comparison to unbound Cas9/gRNA in HIV latent hμglia/HIV (HC69) cells. These findings were also validated qualitatively using fluorescence microscopy to assess NF efficacy against latent HIV in the microglia cells. We believe that CNS delivery of NF (CRISPR/Cas9-gRNA-MENPs) across the BBB certainly will have clinical utility as future personalized nanomedicine to manage neuroHIV/AIDS.
    47 schema:genre research_article
    48 schema:inLanguage en
    49 schema:isAccessibleForFree true
    50 schema:isPartOf N1076246b4d5845a79a6c81317bb8c459
    51 N56046af586dd484aadec41093bcbdb79
    52 sg:journal.1045337
    53 schema:name Magnetically guided non-invasive CRISPR-Cas9/gRNA delivery across blood-brain barrier to eradicate latent HIV-1 infection
    54 schema:pagination 3928
    55 schema:productId N11b009e038e047e8b8cb654637666043
    56 N13e868a548504c8aa39dc12f5412dca5
    57 N87eedeb55fb148d49a6879ccd91f8e7a
    58 Nc5be679288f844bda1c4b78a790386f4
    59 Nf6e73554d970417f85ccc1bf86eb79f3
    60 schema:sameAs https://app.dimensions.ai/details/publication/pub.1112641499
    61 https://doi.org/10.1038/s41598-019-40222-4
    62 schema:sdDatePublished 2019-04-11T13:21
    63 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    64 schema:sdPublisher Nbebac5f747ed4e69ab9c52745c4a483e
    65 schema:url https://www.nature.com/articles/s41598-019-40222-4
    66 sgo:license sg:explorer/license/
    67 sgo:sdDataset articles
    68 rdf:type schema:ScholarlyArticle
    69 N00888156f0d348c8b69a12cc7723aeb1 schema:affiliation https://www.grid.ac/institutes/grid.65456.34
    70 schema:familyName Kaushik
    71 schema:givenName Ajeet
    72 rdf:type schema:Person
    73 N1076246b4d5845a79a6c81317bb8c459 schema:volumeNumber 9
    74 rdf:type schema:PublicationVolume
    75 N11b009e038e047e8b8cb654637666043 schema:name pubmed_id
    76 schema:value 30850620
    77 rdf:type schema:PropertyValue
    78 N13e868a548504c8aa39dc12f5412dca5 schema:name dimensions_id
    79 schema:value pub.1112641499
    80 rdf:type schema:PropertyValue
    81 N1481cf0540aa44f091b75696c6d8af72 rdf:first N84a63af5a7a745209f47821b302f26d4
    82 rdf:rest N4f218ad35507482ab371a9b8184f5608
    83 N188cf31547e64bb4a31dde79d00773bd schema:affiliation https://www.grid.ac/institutes/grid.67105.35
    84 schema:familyName Alvarez-Carbonell
    85 schema:givenName David
    86 rdf:type schema:Person
    87 N26b8edaffbad435ebab50b674e68b226 schema:affiliation https://www.grid.ac/institutes/grid.65456.34
    88 schema:familyName Nair
    89 schema:givenName Madhavan
    90 rdf:type schema:Person
    91 N4f218ad35507482ab371a9b8184f5608 rdf:first N737de65985bb4ad38b3307091d10c42b
    92 rdf:rest N8bc2f0103d174147ad0c71604bb51cb5
    93 N56046af586dd484aadec41093bcbdb79 schema:issueNumber 1
    94 rdf:type schema:PublicationIssue
    95 N5e8bf777d857413cb4d40ffdbcd94d0e schema:affiliation https://www.grid.ac/institutes/grid.264727.2
    96 schema:familyName Khalili
    97 schema:givenName Kamel
    98 rdf:type schema:Person
    99 N737de65985bb4ad38b3307091d10c42b schema:affiliation https://www.grid.ac/institutes/grid.65456.34
    100 schema:familyName Atluri
    101 schema:givenName Venkata
    102 rdf:type schema:Person
    103 N79a3e2a96f4040e29c3f05a98db5751d schema:affiliation https://www.grid.ac/institutes/grid.65456.34
    104 schema:familyName Tiwari
    105 schema:givenName Sneham
    106 rdf:type schema:Person
    107 N84a63af5a7a745209f47821b302f26d4 schema:affiliation https://www.grid.ac/institutes/grid.65456.34
    108 schema:familyName Yndart
    109 schema:givenName Adriana
    110 rdf:type schema:Person
    111 N87eedeb55fb148d49a6879ccd91f8e7a schema:name doi
    112 schema:value 10.1038/s41598-019-40222-4
    113 rdf:type schema:PropertyValue
    114 N8bc2f0103d174147ad0c71604bb51cb5 rdf:first N79a3e2a96f4040e29c3f05a98db5751d
    115 rdf:rest Nbf5aceea20d1468b928ed887c5b05e24
    116 N8d0258b573b2464a8e7e56082adcec15 rdf:first N188cf31547e64bb4a31dde79d00773bd
    117 rdf:rest Nbb291f9ad0404c51a575ad1d4c6a1575
    118 N98be90c5a13e405ba4f92a248daaaf63 rdf:first N26b8edaffbad435ebab50b674e68b226
    119 rdf:rest rdf:nil
    120 Na24811396437406b9d988135316933ae rdf:first Nfe975e4e2e1940a3881eac1d8a300c68
    121 rdf:rest N8d0258b573b2464a8e7e56082adcec15
    122 Nbb291f9ad0404c51a575ad1d4c6a1575 rdf:first N5e8bf777d857413cb4d40ffdbcd94d0e
    123 rdf:rest N98be90c5a13e405ba4f92a248daaaf63
    124 Nbc350842e457476dbb419eacd4a76cd7 rdf:first Nffbb95b1153a4868810137c98d47b6f8
    125 rdf:rest Na24811396437406b9d988135316933ae
    126 Nbebac5f747ed4e69ab9c52745c4a483e schema:name Springer Nature - SN SciGraph project
    127 rdf:type schema:Organization
    128 Nbf5aceea20d1468b928ed887c5b05e24 rdf:first Nd76f83b2014f4778aa01ca579046393f
    129 rdf:rest Nbc350842e457476dbb419eacd4a76cd7
    130 Nc5be679288f844bda1c4b78a790386f4 schema:name readcube_id
    131 schema:value bd9b787c018cb55e60a0b8f6a67390f29cfd8501f68cf4ea3fb6539368fd130e
    132 rdf:type schema:PropertyValue
    133 Nd76f83b2014f4778aa01ca579046393f schema:affiliation https://www.grid.ac/institutes/grid.65456.34
    134 schema:familyName Tomitaka
    135 schema:givenName Asahi
    136 rdf:type schema:Person
    137 Nec80d968be244d7a9e52008cff3daf1f rdf:first N00888156f0d348c8b69a12cc7723aeb1
    138 rdf:rest N1481cf0540aa44f091b75696c6d8af72
    139 Nf6e73554d970417f85ccc1bf86eb79f3 schema:name nlm_unique_id
    140 schema:value 101563288
    141 rdf:type schema:PropertyValue
    142 Nfe975e4e2e1940a3881eac1d8a300c68 schema:affiliation https://www.grid.ac/institutes/grid.65456.34
    143 schema:familyName Jayant
    144 schema:givenName Rahul Dev
    145 rdf:type schema:Person
    146 Nffbb95b1153a4868810137c98d47b6f8 schema:affiliation https://www.grid.ac/institutes/grid.65456.34
    147 schema:familyName Gupta
    148 schema:givenName Purnima
    149 rdf:type schema:Person
    150 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    151 schema:name Medical and Health Sciences
    152 rdf:type schema:DefinedTerm
    153 anzsrc-for:1108 schema:inDefinedTermSet anzsrc-for:
    154 schema:name Medical Microbiology
    155 rdf:type schema:DefinedTerm
    156 sg:grant.2486790 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-019-40222-4
    157 rdf:type schema:MonetaryGrant
    158 sg:grant.2487317 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-019-40222-4
    159 rdf:type schema:MonetaryGrant
    160 sg:grant.2616178 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-019-40222-4
    161 rdf:type schema:MonetaryGrant
    162 sg:grant.3535138 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-019-40222-4
    163 rdf:type schema:MonetaryGrant
    164 sg:grant.4455491 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-019-40222-4
    165 rdf:type schema:MonetaryGrant
    166 sg:grant.5504524 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-019-40222-4
    167 rdf:type schema:MonetaryGrant
    168 sg:journal.1045337 schema:issn 2045-2322
    169 schema:name Scientific Reports
    170 rdf:type schema:Periodical
    171 sg:pub.10.1007/978-3-319-63633-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1099637105
    172 https://doi.org/10.1007/978-3-319-63633-7
    173 rdf:type schema:CreativeWork
    174 sg:pub.10.1007/s00204-015-1504-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1022702690
    175 https://doi.org/10.1007/s00204-015-1504-y
    176 rdf:type schema:CreativeWork
    177 sg:pub.10.1007/s13365-014-0308-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020589574
    178 https://doi.org/10.1007/s13365-014-0308-9
    179 rdf:type schema:CreativeWork
    180 sg:pub.10.1038/491s58a schema:sameAs https://app.dimensions.ai/details/publication/pub.1013453076
    181 https://doi.org/10.1038/491s58a
    182 rdf:type schema:CreativeWork
    183 sg:pub.10.1038/ncomms2717 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018990270
    184 https://doi.org/10.1038/ncomms2717
    185 rdf:type schema:CreativeWork
    186 sg:pub.10.1038/ncomms7413 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053069309
    187 https://doi.org/10.1038/ncomms7413
    188 rdf:type schema:CreativeWork
    189 sg:pub.10.1038/nri3262 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046155496
    190 https://doi.org/10.1038/nri3262
    191 rdf:type schema:CreativeWork
    192 sg:pub.10.1038/s41551-018-0252-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1105103369
    193 https://doi.org/10.1038/s41551-018-0252-8
    194 rdf:type schema:CreativeWork
    195 sg:pub.10.1038/srep02953 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038036933
    196 https://doi.org/10.1038/srep02953
    197 rdf:type schema:CreativeWork
    198 sg:pub.10.1038/srep16277 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009214649
    199 https://doi.org/10.1038/srep16277
    200 rdf:type schema:CreativeWork
    201 sg:pub.10.1038/srep22555 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015116002
    202 https://doi.org/10.1038/srep22555
    203 rdf:type schema:CreativeWork
    204 sg:pub.10.1038/srep25309 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004272211
    205 https://doi.org/10.1038/srep25309
    206 rdf:type schema:CreativeWork
    207 sg:pub.10.1038/srep45663 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084511398
    208 https://doi.org/10.1038/srep45663
    209 rdf:type schema:CreativeWork
    210 sg:pub.10.1186/s12977-017-0335-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1083687350
    211 https://doi.org/10.1186/s12977-017-0335-8
    212 rdf:type schema:CreativeWork
    213 sg:pub.10.3103/s1068335614110025 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024854025
    214 https://doi.org/10.3103/s1068335614110025
    215 rdf:type schema:CreativeWork
    216 https://app.dimensions.ai/details/publication/pub.1079087771 schema:CreativeWork
    217 https://doi.org/10.1002/ange.201506030 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029765980
    218 rdf:type schema:CreativeWork
    219 https://doi.org/10.1002/bip.20998 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050679483
    220 rdf:type schema:CreativeWork
    221 https://doi.org/10.1002/jrs.4206 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013491258
    222 rdf:type schema:CreativeWork
    223 https://doi.org/10.1002/rmv.1778 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010211473
    224 rdf:type schema:CreativeWork
    225 https://doi.org/10.1016/j.addr.2013.09.006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039688958
    226 rdf:type schema:CreativeWork
    227 https://doi.org/10.1016/j.addr.2016.02.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028234926
    228 rdf:type schema:CreativeWork
    229 https://doi.org/10.1016/j.drudis.2006.10.013 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000537417
    230 rdf:type schema:CreativeWork
    231 https://doi.org/10.1016/j.drudis.2017.11.010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092728338
    232 rdf:type schema:CreativeWork
    233 https://doi.org/10.1016/j.jmmm.2003.12.582 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002735411
    234 rdf:type schema:CreativeWork
    235 https://doi.org/10.1016/j.tips.2009.08.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041486814
    236 rdf:type schema:CreativeWork
    237 https://doi.org/10.1016/s0002-9440(10)65476-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038768256
    238 rdf:type schema:CreativeWork
    239 https://doi.org/10.1021/acschemneuro.5b00156 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053919861
    240 rdf:type schema:CreativeWork
    241 https://doi.org/10.1021/ja800023j schema:sameAs https://app.dimensions.ai/details/publication/pub.1055857687
    242 rdf:type schema:CreativeWork
    243 https://doi.org/10.1038/sj.jcbfm.9600330 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023706990
    244 rdf:type schema:CreativeWork
    245 https://doi.org/10.1039/9781788010481 schema:sameAs https://app.dimensions.ai/details/publication/pub.1109459087
    246 rdf:type schema:CreativeWork
    247 https://doi.org/10.1073/pnas.1405186111 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049574595
    248 rdf:type schema:CreativeWork
    249 https://doi.org/10.1093/hmg/ddu125 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037875677
    250 rdf:type schema:CreativeWork
    251 https://doi.org/10.1126/science.1232033 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022072971
    252 rdf:type schema:CreativeWork
    253 https://doi.org/10.1136/jmedgenet-2014-102968 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002742739
    254 rdf:type schema:CreativeWork
    255 https://doi.org/10.1146/annurev.biophys.28.1.1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000201024
    256 rdf:type schema:CreativeWork
    257 https://doi.org/10.1517/17425247.2014.933803 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016798463
    258 rdf:type schema:CreativeWork
    259 https://doi.org/10.2147/ijn.s76517 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028859536
    260 rdf:type schema:CreativeWork
    261 https://doi.org/10.2217/nnm-2018-0005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101241104
    262 rdf:type schema:CreativeWork
    263 https://doi.org/10.3390/jnt1010001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1105950660
    264 rdf:type schema:CreativeWork
    265 https://www.grid.ac/institutes/grid.264727.2 schema:alternateName Temple University
    266 schema:name Department of Neuroscience, Lewis Katz School of Medicine, Temple University, 19140, Philadelphia, USA
    267 rdf:type schema:Organization
    268 https://www.grid.ac/institutes/grid.65456.34 schema:alternateName Florida International University
    269 schema:name Department of Immunology and Nano-Medicine, Center for Personalized Nanomedicine, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
    270 rdf:type schema:Organization
    271 https://www.grid.ac/institutes/grid.67105.35 schema:alternateName Case Western Reserve University
    272 schema:name Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH, USA
    273 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...