A controlled, Phase 1 clinical trial to evaluate the safety and effects in HIV-1 infected humans of autologous lymphocytes transduced with a ribozyme that cleaves HIV-1 RNA

Flossie Wong-Staal, Eric M. Poeschla, David J. Looney

Research output: Contribution to journalArticle

140 Scopus citations

Abstract

This Phase I study, 'Ribozyme Gene Therapy of HIV-1 Infection', is a prospective, open-label trial of infusion of autologous gene-altered cells into asymptomatic HIV-1 seropositive individuals. The objectives of this trial are to test the safety, feasibility, and potential efficacy of T-cell ribozyme gene therapy of HIV-1 infection. To accomplish this, autologous CD8-depleted mononuclear cells are transduced with ribozyme expressing or control murine retroviral vectors, expanded ex vivo, and and infused. Subjects are monitored intensively to determine effects of infusion on HIV burden and replication. In addition, in vivo survival of control and ribozyme transduced cells is followed in an effort to obtain evidence of proof of concept. A unique strategy of sample blinding is introduced in this protocol, wherein both subject and control specimens are supplied to the research laboratory as coded samples, spiking blood from HIV seropositive volunteers matched for CD4 lymphocyte count with known but varying numbers of cells transduced with each vector. While this study is still in progress, preliminary results indicate that infusion of gene-altered, activated T-cells in HIV infected patients is safe, and that transduced cells can persist for long intervals in HIV-infected subjects. Results also suggest ribozyme transduced cells may possess a survival advantage in vivo.

Original languageEnglish (US)
Pages (from-to)2407-2425
Number of pages19
JournalHuman gene therapy
Volume9
Issue number16
DOIs
StatePublished - Nov 1 1998

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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