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
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
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
Based on these results a clinical study protocol has been developed
and is awaiting approval from the FDA and other regulatory agencies,