title: Long-term survival and concomitant gene expression of ribozyme-transduced CD4+ T-lymphocytes in HIV-infected patients.
abstract: BACKGROUND
  An anti-HIV-1 tat ribozyme, termed Rz2, has been shown to inhibit HIV-1 infection/replication and to decrease HIV-1-induced pathogenicity in T-lymphocyte cell lines and normal peripheral blood T-lymphocytes. We report here the results of a phase I gene transfer clinical trial using Rz2.
  
  
  METHODS
  Apheresis was used to obtain a peripheral blood cell population from each of four HIV-negative donors. After enrichment for CD4+ T-lymphocytes, ex vivo expansion and genetic manipulation (approximately equal aliquots of the cells were transduced with the ribozyme-containing (RRz2) and the control (LNL6) retroviral vector), these cells were infused into the corresponding HIV-1-positive twin recipient. Marking was assessed over an initial 24-week period and in total over an approximate 4-year period.
  
  
  RESULTS
  The gene transfer procedure was shown to be safe, and technically feasible. Both RRz2- and LNL6-gene-containing peripheral blood mononuclear cells (PBMC) were detected at all time points examined to 4 years. There was concomitant gene construct expression in the absence of the need for ex vivo peripheral blood cell stimulation and there was no evidence of immune elimination of the neoR T-lymphocytes nor of silencing of the Moloney murine leukemia virus long terminal repeat.
  
  
  CONCLUSIONS
  The proof of principle results reported here demonstrate safety and feasibility of this type of gene transfer approach. While not specifically tested, T-lymphocytes containing an anti-HIV gene construct may impact on HIV-1 viral load and CD4+ T-lymphocyte count, potentially representing a new therapeutic modality for HIV-1 infection.
authors.affiliation: Johnson and Johnson Research Pty Limited, Locked Bag 4555, Strawberry Hills, Sydney, NSW Australia 2012. jmacpher@medau.jnj.com
authors.forename: Janet L
authors.initials: JL
authors.lastname: Macpherson
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Boyd
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Arndt
authors.forename: Alison V
authors.initials: AV
authors.lastname: Todd
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Fanning
authors.forename: Julie A
authors.initials: JA
authors.lastname: Ely
authors.forename: Fiona
authors.initials: F
authors.lastname: Elliott
authors.forename: Alison
authors.initials: A
authors.lastname: Knop
authors.forename: Mitch
authors.initials: M
authors.lastname: Raponi
authors.forename: John
authors.initials: J
authors.lastname: Murray
authors.forename: Wayne
authors.initials: W
authors.lastname: Gerlach
authors.forename: Lun-Quan
authors.initials: LQ
authors.lastname: Sun
authors.forename: Ronald
authors.initials: R
authors.lastname: Penny
authors.forename: Geoff P
authors.initials: GP
authors.lastname: Symonds
authors.forename: Andrew
authors.initials: A
authors.lastname: Carr
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004200:Diseases in Twins / Q000276:immunology / Q000628:therapy*; D015870:Gene Expression; D015756:Genes, tat / Q000502:physiology; D015316:Genetic Therapy; D005822:Genetic Vectors; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D016337:RNA, Catalytic / Q000235:genetics / Q000494:pharmacology*; D012190:Retroviridae / Q000235:genetics; D015996:Survival Rate; D013997:Time Factors; D014161:Transduction, Genetic; D014430:Twins, Monozygotic
chemical_list: D016337:RNA, Catalytic