Acquired immunodeficiency syndrome is caused by a human immunodeficiency virus (HIV) that infects and destroys helper T- lymphocytes. These experiments are designed to test whether RNA sequences complimentary to portions of the HIV genome (anti-sense RNA) can block HIV replication or gene expression thereby creating T-lymphocytes that are resistant to the cytopathic affects of HIV. Segments of the HIV genome are placed in a reversed or anti-sense transcriptional orientation in a transcriptional unit that includes a strong promoter and appropriate RNA processing signals. Such anti-sense transcriptional units are introduced into T-lymphoid cell lines in vitro and expression of the anti-sense sequences documented by appropriate molecular analysis. Cell clones that express the anti- sense sequences at high levels will be tested to determine whether inhibition of HIV replication has been achieved. A systematic approach utilizing DNA fragments from various portions of the HIV genome under the control of several strong promoters is planned. If a effective anti-sense transcriptional unit is created, it will be incorporated into a recombinant retrovirus in an effort to facilitate transfer and expression in primary T-lymphocytes from infected patients.
