Efficient gene transfer into human monocyte-derived macrophages using defective lentiviral vectors.

Y. Lu, C. Liu, L. Zeng, Z. Lin, S. Dewhurst, S. Gartner, V. Planelles

Research output: Contribution to journalArticle

Abstract

Gene therapy is a promising approach for the treatment of neurological disorders. However, current approaches to gene transfer in the central nervous system (CNS) are limited by the lack of effective, but non-invasive methods to deliver transgenes across the blood-brain barrier (BBB). In an effort to begin to explore the use of migratory monocytes as vehicles for delivery of therapeutic and antiviral genes into the CNS, we have utilized three HIV-based transfer vectors encoding cis-acting elements but lacking either structural genes (gag/pol and env), most accessory genes (vif, vpr and nef) and/or rev. These defective lentiviral vectors (DLV) encode the green fluorescent protein (GFP), display potent antiviral activity in CD4+ lymphocytes and can be mobilized by wild-type HIV-1 DLV were generated by transient transfection of 293T cells. Vector titers ranged from 4.2-6.6 x 10(6) infectious units (IU)/ml prior to concentration (by ultracentrifugation) and were equal to or higher than 1 x 10(9) IU/ml after concentration. Primary human monocyte-derived macrophages (MDM) were exposed to DLV resulting in efficiencies of transduction ranging from 14 to 26%. GFP expression in transduced MDM remained stable for more than 8 weeks without apparent cytopathic effect. Given the previously reported antiviral activities of these DLV and their lack of cytopathic effects on primary MDM, it may be possible to use these vectors to inhibit HIV-1 replication within the CNS.

Original languageEnglish (US)
Pages (from-to)1151-1156
Number of pages6
JournalCellular and molecular biology (Noisy-le-Grand, France)
Volume49
Issue number7
StatePublished - Nov 2003
Externally publishedYes

Fingerprint

Gene transfer
Macrophages
Antiviral Agents
Central Nervous System
Green Fluorescent Proteins
HIV-1
nef Genes
vif Genes
pol Genes
gag Genes
Neurology
Genes
vpr Genes
env Genes
HEK293 Cells
Ultracentrifugation
Nervous System Diseases
Blood-Brain Barrier
Transgenes
Genetic Therapy

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Lu, Y., Liu, C., Zeng, L., Lin, Z., Dewhurst, S., Gartner, S., & Planelles, V. (2003). Efficient gene transfer into human monocyte-derived macrophages using defective lentiviral vectors. Cellular and molecular biology (Noisy-le-Grand, France), 49(7), 1151-1156.

Efficient gene transfer into human monocyte-derived macrophages using defective lentiviral vectors. / Lu, Y.; Liu, C.; Zeng, L.; Lin, Z.; Dewhurst, S.; Gartner, S.; Planelles, V.

In: Cellular and molecular biology (Noisy-le-Grand, France), Vol. 49, No. 7, 11.2003, p. 1151-1156.

Research output: Contribution to journalArticle

Lu, Y, Liu, C, Zeng, L, Lin, Z, Dewhurst, S, Gartner, S & Planelles, V 2003, 'Efficient gene transfer into human monocyte-derived macrophages using defective lentiviral vectors.', Cellular and molecular biology (Noisy-le-Grand, France), vol. 49, no. 7, pp. 1151-1156.
Lu, Y. ; Liu, C. ; Zeng, L. ; Lin, Z. ; Dewhurst, S. ; Gartner, S. ; Planelles, V. / Efficient gene transfer into human monocyte-derived macrophages using defective lentiviral vectors. In: Cellular and molecular biology (Noisy-le-Grand, France). 2003 ; Vol. 49, No. 7. pp. 1151-1156.
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