312   Gene Delivery Protects from HIV-1In Vivo.

D. S. Strayer*¹, M. Petoello-Mantovani², R. J. Pomerantz¹, and H. Goldstein².
¹Jefferson Med. Coll., Philadelphia, PA and²Albert Einstein Coll. of Med., Bronx, NY.

Background:Despite success in inhibiting HIV-1 in vitro , gene delivery has not been useful against HIV-1 in vivo . We report here that an SV40-derived vector (rSV40), given in vivo , can inhibit HIV-1 in vivo .

Methods:SV(Aw), a Tag-deleted replication-crippled rSV40 vector, carries Aw, a single-chain Fv antibody (SFv) against HIV-1 integrase (IN), with a CMV promoter. Human fetal thymus grafts under renal capsules of SCID mice were treated after implantation with SV(Aw). Animals were then challenged in vivo by inoculating a clinical isolate of HIV-1. Protection from HIV-1 was assessed by explanting grafts into a coculture assay and measuring p24 levels in these cultures.

Results:One inoculation of the thymic implant transduced 80—90% of the cells within the graft, as measured by immunostaining. Coculture assay yielded mean p24 values of 375 ± 100 ng/ml for SV(Aw)-transduced grafts. Grafts from control animals yielded 1875 ± 614 ng/ml (treated with unrelated rSV40) and 3125 ± 0 ng/ml (untransduced) p24. SV(Aw)-treated grafts were significantly protected (P < 0.04 by Wilcoxon signed rank test) compared to both controls.

Conclusions: In vivo gene delivery by rSV40 vectors is very efficient. We exploited these vectors to deliver anti- IN SFv and to protect human tissue grafts in SCID-hu mice from in vivo challenge with HIV-1.