The rapid evolutionary rate of HIV-1 has lead to the emergence of multi-drug resistant variants, emphasizing the need for novel inhibitory methods. One such method could be based upon inhibiting viral gene expression through disruption of HIV-1 RNA processing. A means of accomplishing this goal is through use of modified U1snRNA variants that target highly conserved regions of HIV-1 at its terminal exon and prevent 3’ end formation. The modification consists of a 10-nucleotide substitution at the 5’ end complementary to the conserved HIV-1 regions. When modified U1snRNA targeted to HIV-1 were cotransfected with replication deficient HIV-1 proviruses, western blot indicated a specific and significant reduction in the level of viral protein production (p24 and gp120), while U1 constructs that lacked complementary sequences had no effect on HIV-1 protein expression. To further investigate targeted U1snRNA inhibitory effects on HIV-1, efforts are currently underway to determine if this approach has the ability to suppress protein expression in a gene therapeutic model. To date, suppression of viral protein production has reached 50% when tested with a moderately inhibitory U1snRNA. If shown to be effective, such an inhibition would be increased with the use of combinatory modified U1snRNA constructs producing a synergistic effect.

The rapid evolutionary rate of HIV-1 has lead to the emergence of multi-drug resistant variants, emphasizing the need for novel inhibitory methods. One such method could be based upon inhibiting viral gene expression through disruption of HIV-1 RNA processing. A means of accomplishing this goal is through use of modified U1snRNA variants that target highly conserved regions of HIV-1 at its terminal exon and prevent 3’ end formation. The modification consists of a 10-nucleotide substitution at the 5’ end complementary to the conserved HIV-1 regions. When modified U1snRNA targeted to HIV-1 were cotransfected with replication deficient HIV-1 proviruses, western blot indicated a specific and significant reduction in the level of viral protein production (p24 and gp120), while U1 constructs that lacked complementary sequences had no effect on HIV-1 protein expression. To further investigate targeted U1snRNA inhibitory effects on HIV-1, efforts are currently underway to determine if this approach has the ability to suppress protein expression in a gene therapeutic model. To date, suppression of viral protein production has reached 50% when tested with a moderately inhibitory U1snRNA. If shown to be effective, such an inhibition would be increased with the use of combinatory modified U1snRNA constructs producing a synergistic effect.