Targeting HIV Infected Cells with Pro-Apoptotic siRNAs
Authors:Katelyn Peloza, Mayumi Takahashi
Mentor:John Burnett, Assistant Research Professor, Beckman Research Institute, City of Hope
Small interfering RNAs (siRNA) are a fascinating field of research for therapeutics development because of the promise of specific control and manipulation of gene expression. Current HIV treatments, while successful at mitigating the progression to AIDS, are not able to eradicate the virus from the body. Targeting HIV infected cells with toxic siRNAs may provide a method to eliminate these dangerous cells. Cells were treated with apoptosis inducing siRNAs to initiate the cells’ suicide mechanism. HIV susceptible T-cells were transfected with dicer substrate siRNAs designed to knockdown the following apoptosis inhibitors: Bcl-xl, Bcl-2. Survivin, and Birc2. All siRNAs were found capable of decreasing target mRNA levels compared to T-cells treated with non-toxic siRNAs. Furthermore, several siRNAs were found to induce apoptosis, with Bcl-xl being the most successful. Most interesting, combinatorial siRNA treatments yielded the greatest induction of apoptosis, and exhibited a synergistic mechanism, with 25% of cells undergoing apoptosis for all combinational siRNA treatments. These siRNAs prove promising in toxicity and provide a basis for further testing with target specific aptamers.