Transfer of an Anti-HIV-1 Ribozyme Gene into Primary Human Lymphocytes

Mark C. Leavitt, Mang yu, Osamu Yamada, Günter Kraus, David Looney, Eric Poeschla, Flossie Wong-Staal

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98 Scopus citations


We reported previously that human CD4+ T cell lines stably expressing a hairpin ribozyme targeted to the human immunodeficiency virus type 1 (HIV-1) U5 leader sequence were resistant to challenge with diverse HIV-l viral clones and clinical isolates (Yamada et al., 1994). To simulate more closely the in vivo infection process for investigations of anti-HIV-1 ribozyme gene therapy, we developed a system to transfer this ribozyme gene into freshly isolated human peripheral blood lymphocytes (PBLs) using a murine retrovirus vector. Following transduction and G418 selection, human PBLs from multiple donors expressed the ribozyme and resisted challenge by HIV-1 viral clones and clinical isolates, while control vector-transduced PBLs remained fully permissive for HIV-1 infection. No inhibition of an HIV-2 clone lacking the target was seen in ribozyme-expressing PBLs. Ribozyme expression had no effect on viability or proliferation kinetics of the primary lymphocytes. This study is the first demonstration in primary human T cells of resistance to HIV-1 infection conferred by gene transfer. A human clinical trial is in development to test further the safety and efficacy of this ribozyme in PBLs of HlV-1-infected patients in vivo.

Original languageEnglish (US)
Pages (from-to)1115-1120
Number of pages6
JournalHuman gene therapy
Issue number9
StatePublished - Sep 1 1994

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics


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