Screening for small molecule inhibitors of HIV-1 Gag expression

- Outline of cell based assays for the identification of small molecule modulators of HIV-1 RNA processing.
- Outline of procedures for the validation of compounds hits.
- Summary of compounds demonstrated to modulate RNA splicing in HIV-1 and other systems.

The control of RNA processing plays an important role in the nature and quantity of protein generated from mammalian genes. Consequently, efforts to manipulate RNA processing have the capacity to significantly impact gene function. Although multiple strategies have been developed to alter splice site selection using oligonucleotide occlusion of splice sites or splicing regulatory elements, systemic delivery of such agents remains problematic. Outlined in this chapter is a protocol to screen for small molecule inhibitors of HIV-1 Gag expression that have been subsequently determined to modulate viral RNA processing. Identification and characterization of such RNA processing modulators offers the potential for the development of therapeutic lead compounds or probes for investigating the mechanism underlying the regulation of select RNA processing events.