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(NAS Colloquium) Genetic Engineering of Viruses and Viral Vectors (1996) / Chapter Skim
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Development of HIV vectors for anti-HIV gene therapy
Pages 11395-11399

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From page 11395...
... Medicine and Biology, Mail Code 0665, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0665 ABSTRACT Current gene therapy protocols for HIV infection use transfection or marine retrovirus mediated transfer of antiviral genes into CD4+ T cells or CD34+ progenitor cells ex viva, followed by infusion of the gene altered cells into autologous or syngeneic/allogeneic recipients. While these studies are essential for safety and feasibility testing, several limitations remain: long-term reconstitution of the immune system is not effected for lack of access to the macrophage reservoir or the pluripotent stem cell population, which is usually quiescent, and ex vivo manipulation of the target cells will be too expensive and impractical for global application.
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From page 11396...
... Our laboratory has concentrated on the hairpin ribozyme (19-27~; other groups have employed hammerhead ribozymes for antiviral studies (28-31~. Using Moloney murine leukemia virus-based retroviral vectors for delivery, hairpin ribozymes have been shown to confer protection from HIV-1 infection of T-cell lines, primary T cells, and macrophage-like progeny of CD34+ hematopoietic progenitor cells (19-25~.
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From page 11397...
... This paper describes our progress in developing stable cell lines capable of expressing the full complement of HIV-1 and HIV-2 proteins in bans and the development of HIV-based vectors that can be packaged in these lines or by pseudotyping with VSV-G. Packaging Cell Lines To devise HIV-1MN and HIV-2KR packaging constructs to supply HIV proteins in bans, deletions of 37 and 61 bp respectively were made in the regions between the major 5' splice donor and the gag gene initiation codon (Fig.
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From page 11398...
... or that of the producer cells which allowed expression of high titers of infectious vectors. Pseudotyped HIV-2 vectors were generated by transient triple cotransfection of a packaging construct with an additional deletion in the env gene, the vector plasmid, and a plasmid encoding VSV-G under control of the hCMV promoter (kindly supplied by T
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From page 11399...
... (1993) in Reverse Transcriptase, eds.
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Key Terms

  • cell lines
  • packaging cell
  • gene transfer
  • hiv infection
  • stomatitis virus

  • stem cells
  • virus glycoprotein
  • progenitor cells
  • vesicular stomatitis
  • moloney murine

  • murine leukemia
  • stable expression
  • hematopoietic progenitor
  • gene delivery
  • hiv vectors

  • altered cells
  • retroviral vectors
  • packaging construct
  • stable cell
  • vivo transduction

  • human macrophages
  • gag gene
  • cell line
  • genetic regulation
  • packaging lines

  • stem cell
  • hiv envelopes
  • terminal repeat
  • rev response
  • leukemia virus


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