title: 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.
abstract: This Phase I study, "Ribozyme Gene Therapy of HIV-1 Infection" (UCSD HSC #971072, FDA BB-IND 6405), 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.
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla 92093, USA.
authors.forename: F
authors.initials: F
authors.lastname: Wong-Staal
authors.forename: E M
authors.initials: EM
authors.lastname: Poeschla
authors.forename: D J
authors.initials: DJ
authors.lastname: Looney
mesh_terms: D002985:Clinical Protocols; D017321:Clinical Trials, Phase I as Topic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1; D006801:Humans; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000502:physiology*; D016337:RNA, Catalytic / Q000235:genetics / Q000494:pharmacology*
chemical_list: D016337:RNA, Catalytic