Generation of Genetic Suppressor Elements Against HIV

Somatic gene therapy of bone marrow stem cells has been proposed as an alternative to conventionalAIDS. Successful inhibition of HIV replication using ribozymes, antisense oligonucleotides, RNA-decodominant-negative mutants has been reported. We have developed a new technology for the efficient gesuppressors represented by antisense RNA and dominant-negative mutants. It is based on the functionasuppressor elements (GSEs) from a random fragment library generated from a gene or a genome of interhas been validated in two model systems: The selection of GSEs, derived from the lambda phage genomebacterial resistance to phage-mediated lysis and-also the isolation of USEs from the human topoisomeconferred etoposide resistance to human cells. We have generated USE libraries from the HIV-l genomeputative USEs capable of protecting human cells from HIV-mediated cytopathicity. Our aim is to fullycurrent pool of anti-HIV USE candidates by further selection and to also develop an alternative GSEthat will address limitations identified in preliminary studies. In addition, we will evaluate "GSE-multiple, characterized, anti-HIV elements that inhibit different stages of the viral life cycle. Thpotential candidates for somatic gene therapy of HIV infected cells.