Potential nuclease-based strategies for HIV gene therapy

Gene therapy for HIV (human immunodeficiency virus) involves the introducti on of a therapeutic gene into the infected individual for the purposes of r educing viral load and ultimately reconstituting a healthy immune system. C linical trials for HIV gene therapy have not yet reported therapeutic benef it. In addition to improving the efficiency of gene delivery and the mainte nance of gene expression, better therapeutic genes must be designed before this therapy becomes available to patients. A new class of therapeutic gene s expressing nucleases may be designed. These nucleases may be classified i nto three categories based on their mode of action: (i) 'targeted nucleases ' for specifically cleaving HIV RNA within the cell, (ii) 'colocalized nucl eases' for cleaving HIV genomic DNA or RNA present within the cell or proge ny virus, and (iii) 'cytotoxic nucleases' for conferring selective toxicity to HIV-infected cells. The focus of this review is on the design and appli cation of these nucleases for HIV gene therapy.