MONTREAL, Canada--The centerpiece of efforts to develop gene therapy to treat human immunodeficiency virus (HIV) disease at the University of California, San Diego, has been the use of ribozymes, Flossie Wong-Staal, PhD, said at the 19th International Congress of Chemotherapy.
Dr. Wong-Staal's group at San Diego has developed a "hairpin ribozyme," which, based on preclinical studies, is about to be tested to evaluate its safety and feasibility for use as gene therapy in HIV-infected persons, she reported.
Initially, Dr. Wong-Staal explained, ribozymes were selected because they have several major advantages. Ribozymes are small RNA molecules having the dual properties of an antisense molecule, because they recognize the substrate through sequence complementarity and also have the ability to cleave substrate RNA and permanently inactivate it.
Furthermore, because ribozymes are small molecules, it is possible to make combinations of these genes and deliver them in a single delivery system, a factor essential to an effective antiviral strategy.
The hairpin ribozyme, itself, Dr. Wong-Staal continued, has been shown to cleave HIV-1 RNA, suppressing the replication of diverse strains of HIV-1, including clinical isolates.
Furthermore, studies in human T-cell lines and primary T cells from normal donors demonstrated that the hairpin ribozyme can be transduced with the primary lymphocytes, making them resistant to both the infective and cytopathic effects of HIV-1 strains. This resulted in a 4 log reduction in virus titer, Dr. Wong-Staal said.
Based on these results a clinical study protocol has been developed and is awaiting approval from the FDA and other regulatory agencies, she said.