SELF-INACTIVATING LENTIVIRUS VECTOR FOR SAFE AND EFFICIENT IN-VIVO GENE DELIVERY

In vivo transduction of nondividing cells by human immunodeficiency vi rus type 1 (HTV-1)-based vectors results in transgene expression that is stable over several months. However, the use of HIV-1 vectors raise s concerns about their safety. Here we describe a self-inactivating HI V-1 vector with a 400 nucleotide deletion in the 3' long terminal repe at (LTR). The deletion, which includes the TATA box, abolished the LTR promoter activity but did not affect vector titers or transgene expre ssion in vitro. The self-inactivating vector transduced neurons in viv o as efficiently as a vector with full-length LTRs. The inactivation d esign achieved in this work improves significantly the biosafety of HI V-derived vectors, as it reduces the likelihood that replication-compe tent retroviruses will originate in the vector producer and target cel ls, and hampers recombination with wild-type HIV in an infected host. Moreover, it improves the potential performance of the vector by remov ing LTR sequences previously associated with transcriptional interfere nce and suppression in vivo and by allowing the construction of more-s tringent tissue-specific or regulatable vectors.