The development of effective delivery systems for therapeutics to the CNS is critical for AIDS patients with AIDS Dementia Complex-associated dysfunction. Practical treatments for ADC may be more effective if enacted locally within the CNS to avoid the problems associated with systemic exposure to bioactive therapeutics. Encapsidated replicons are proposed to meet these criteria, because they have an inherent capacity to traverse the blood-brain barrier, which permits localized and non-invasive delivery to the CNS. The studies in this proposal will examine the pharmacokinetics of replicon transmission across the BBB in mice and rats. Further studies will employ a replicon vector encoding TGFB to address the ability of replicons to express bioactive cytokines within the CNS. The proposed experiments will evaluate expression of TGFB directly from CNS tissue of mice and will also measure bioactivity of the TGFB by analysis of induction of specific genes know to be responsive to TGFB. Phase II studies will apply this technology to a SCID mouse model for ADC through testing of the therapeutic benefits of replicons encoding TGFB or other immunosuppressive cytokines.
NOT AVAILABLE
