DOI: 10.1128/jvi.72.12.9873-9880.1998. Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery

Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery

10.1128/jvi.72.12.9873-9880.1998

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

ABSTRACT In vivo transduction of nondividing cells by human immunodeficiency virus type 1 (HIV-1)-based vectors results in transgene expression that is stable over several months. However, the use of HIV-1 vectors raises concerns about their safety. Here we describe a self-inactivating HIV-1 vector with a 400-nucleotide deletion in the 3′ long terminal repeat (LTR). The deletion, which includes the TATA box, abolished the LTR promoter activity but did not affect vector titers or transgene expression in vitro. The self-inactivating vector transduced neurons in vivo as efficiently as a vector with full-length LTRs. The inactivation design achieved in this work improves significantly the biosafety of HIV-derived vectors, as it reduces the likelihood that replication-competent retroviruses will originate in the vector producer and target cells, and hampers recombination with wild-type HIV in an infected host. Moreover, it improves the potential performance of the vector by removing LTR sequences previously associated with transcriptional interference and suppression in vivo and by allowing the construction of more-stringent tissue-specific or regulatable vectors.

Bibliography

Zufferey, R., Dull, T., Mandel, R. J., Bukovsky, A., Quiroz, D., Naldini, L., & Trono, D. (1998). Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery. Journal of Virology, 72(12), 9873â9880.

Authors 7

Romain Zufferey (first)
Thomas Dull (additional)
Ronald J. Mandel (additional)
Anatoly Bukovsky (additional)
Dulce Quiroz (additional)
Luigi Naldini (additional)
Didier Trono (additional)

References 31 Referenced 1,478

Dates

Type	When
Created	5 years, 7 months ago (Dec. 31, 2019, 1:05 p.m.)
Deposited	3 years, 5 months ago (March 4, 2022, 9:41 p.m.)
Indexed	5 days, 10 hours ago (Aug. 19, 2025, 6:12 a.m.)
Issued	26 years, 8 months ago (Dec. 1, 1998)
Published	26 years, 8 months ago (Dec. 1, 1998)
Published Print	26 years, 8 months ago (Dec. 1, 1998)

Funders 0

None

BibTeX

@article{Zufferey_1998, title={Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery}, volume={72}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.72.12.9873-9880.1998}, DOI={10.1128/jvi.72.12.9873-9880.1998}, number={12}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Zufferey, Romain and Dull, Thomas and Mandel, Ronald J. and Bukovsky, Anatoly and Quiroz, Dulce and Naldini, Luigi and Trono, Didier}, year={1998}, month=dec, pages={9873–9880} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        19
      ]
    ],
    "date-time": "2025-08-19T10:12:07Z",
    "timestamp": 1755598327071
  },
  "reference-count": 31,
  "publisher": "American Society for Microbiology",
  "issue": "12",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            1998,
            12,
            1
          ]
        ],
        "date-time": "1998-12-01T00:00:00Z",
        "timestamp": 912470400000
      },
      "content-version": "tdm",
      "delay-in-days": 0,
      "URL": "https://journals.asm.org/non-commercial-tdm-license"
    }
  ],
  "content-domain": {
    "domain": [
      "journals.asm.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        1998,
        12
      ]
    ]
  },
  "abstract": "<jats:title>ABSTRACT</jats:title>\n          <jats:p>In vivo transduction of nondividing cells by human immunodeficiency virus type 1 (HIV-1)-based vectors results in transgene expression that is stable over several months. However, the use of HIV-1 vectors raises concerns about their safety. Here we describe a self-inactivating HIV-1 vector with a 400-nucleotide deletion in the 3\u2032 long terminal repeat (LTR). The deletion, which includes the TATA box, abolished the LTR promoter activity but did not affect vector titers or transgene expression in vitro. The self-inactivating vector transduced neurons in vivo as efficiently as a vector with full-length LTRs. The inactivation design achieved in this work improves significantly the biosafety of HIV-derived vectors, as it reduces the likelihood that replication-competent retroviruses will originate in the vector producer and target cells, and hampers recombination with wild-type HIV in an infected host. Moreover, it improves the potential performance of the vector by removing LTR sequences previously associated with transcriptional interference and suppression in vivo and by allowing the construction of more-stringent tissue-specific or regulatable vectors.</jats:p>",
  "DOI": "10.1128/jvi.72.12.9873-9880.1998",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2019,
        12,
        31
      ]
    ],
    "date-time": "2019-12-31T18:05:48Z",
    "timestamp": 1577815548000
  },
  "page": "9873-9880",
  "update-policy": "http://dx.doi.org/10.1128/asmj-crossmark-policy-page",
  "source": "Crossref",
  "is-referenced-by-count": 1478,
  "title": "Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery",
  "prefix": "10.1128",
  "volume": "72",
  "author": [
    {
      "given": "Romain",
      "family": "Zufferey",
      "sequence": "first",
      "affiliation": [
        {
          "name": "<!--label omitted: 1-->Department of Genetics and Microbiology, University of Geneva Medical School, Geneva, Switzerland,1 and"
        }
      ]
    },
    {
      "given": "Thomas",
      "family": "Dull",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 2-->Cell Genesys, Foster City, California2"
        }
      ]
    },
    {
      "given": "Ronald J.",
      "family": "Mandel",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 2-->Cell Genesys, Foster City, California2"
        }
      ]
    },
    {
      "given": "Anatoly",
      "family": "Bukovsky",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 2-->Cell Genesys, Foster City, California2"
        }
      ]
    },
    {
      "given": "Dulce",
      "family": "Quiroz",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 2-->Cell Genesys, Foster City, California2"
        }
      ]
    },
    {
      "given": "Luigi",
      "family": "Naldini",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 2-->Cell Genesys, Foster City, California2"
        }
      ]
    },
    {
      "given": "Didier",
      "family": "Trono",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "<!--label omitted: 1-->Department of Genetics and Microbiology, University of Geneva Medical School, Geneva, Switzerland,1 and"
        }
      ]
    }
  ],
  "member": "235",
  "reference": [
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.15.3.1545"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.71.9.6641-6649.1997"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0006-291X(92)91197-X"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/307241a0"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/mcb.11.3.1624-1630.1991"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.84.5.1197"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.72.11.8463-8471.1998"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1182/blood.V83.1.43.43"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1099/0022-1317-74-1-39"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0042-6822(92)90067-Y"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1182/blood.V84.10.3394.bloodjournal84103394"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.84.8.2406"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.71.9.7128-7131.1997"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ng1197-314"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.68.5.3163-3174.1994"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2830675"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.272.5259.263"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.93.21.11382"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.66.3.1336-1343.1992"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.68.11.7060-7066.1994"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/322562a0"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/17.6.1728"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.65.5.2314-2319.1991"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0042-6822(83)90107-1"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1990.tb07638.x"
    },
    {
      "key": "e_1_3_2_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.88.6.2108"
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/mcb.12.9.3699-3705.1992"
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1089/hum.1996.7.2-159"
    },
    {
      "key": "e_1_3_2_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.84.15.5197"
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.83.10.3194"
    },
    {
      "key": "e_1_3_2_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nbt0997-871"
    }
  ],
  "container-title": "Journal of Virology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/JVI.72.12.9873-9880.1998",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/JVI.72.12.9873-9880.1998",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        3,
        5
      ]
    ],
    "date-time": "2022-03-05T02:41:27Z",
    "timestamp": 1646448087000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://journals.asm.org/doi/10.1128/JVI.72.12.9873-9880.1998"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1998,
        12
      ]
    ]
  },
  "references-count": 31,
  "journal-issue": {
    "issue": "12",
    "published-print": {
      "date-parts": [
        [
          1998,
          12
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1128/JVI.72.12.9873-9880.1998"
  ],
  "URL": "http://dx.doi.org/10.1128/JVI.72.12.9873-9880.1998",
  "relation": {},
  "ISSN": [
    "0022-538X",
    "1098-5514"
  ],
  "subject": [],
  "container-title-short": "J Virol",
  "published": {
    "date-parts": [
      [
        1998,
        12
      ]
    ]
  },
  "assertion": [
    {
      "value": "1998-06-01",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "1998-08-13",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "1998-12-01",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}