Important note: Information in this article was accurate in August 2000. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, August 7, 2000
Prepared by AIDS Weekly editors from staff and other reports
NewsRx -- A novel therapy for the treatment of HIV infection is being developed that incorporates ribozymes and stem cells.
Seeking to genetically alter hematopoietic stem cells with anti-HIV catalytic RNAs (ribozymes), J. Rossi and colleagues from several institutions in California, reported, "Our hypothesis is that stable transduction of pluripotent hematopoietic stem cells by ribozyme expressing vectors followed by engraftment of these cells in the marrow, will ultimately provide a population of HIV-1 resistant T cells, monocytes, and dendritic cells.
"To test this, we have initiated a clinical trial involving HIV-1 infected individuals who have AIDS related lymphoma using vectors harboring ribozyme or vector backbone alone transduced into their stem cells."
Rossi et al. presented data from their study at the 10th European Congress of Clinical Microbiology and Infectious Diseases, held in Stockholm, Sweden. The title of their presentation was "Ribozyme and stem cell gene therapy for the treatment of HIV infection."
The researchers transduced hammerhead ribozymes targeting the HIV-1 tat and rev transcripts into the backbone of a murine retroviral vector. The vector was then used to infect primary hematopoietic progenitor cells from the HIV-1 infected individuals.
They reported that the ribozymes were expressed as a polycistronic transcript from the long terminal repeat (LTR) of the LN retroviral vector.
To parallel their clinical studies, Rossi et al. are also testing new strategies for ribozyme-targeted colocalization using chimeric RNA molecules, they said. These molecules harbor the ribozymes of interest tethered to sequences. The sequences then direct the ribozymes to discrete intracellular localizations, they explained.
"The clinical trial studies have demonstrated a selective survival of ribozyme expressing cells within a period of several weeks following bone marrow transplantation and long-term engraftment in at least one patient," concluded Rossi et al. "Our new chimeric ribozyme localization studies demonstrate that a nucleolar-localized ribozyme is a potent inhibitor of HIV-1.
"Ribozyme mediated gene therapy for the treatment of HIV-1 infection is feasible utilizing hematopoietic stem cells. Potent inhibition of HIV-1 infection by a nucleolar ribozyme suggests nucleolar trafficking of HIV-1 RNAs, opening new targets for anti-HIV-1 strategies."
The corresponding author for this study is J. Rossi, Department of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, California, USA.
Key points reported in this study are:
This article was prepared by AIDS Weekly editors from staff and other reports.
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