In search of more effective cancer treatments, inventors in Dr. Xiaowei Wang’s lab at Washington University School of Medicine have developed artificial interference RNA (aiRNA). aiRNA is a patented chimeric RNAi that combines the multi-target abilities of miRNAs and the robust regulation effects of siRNAs for a potentially more effective and nontoxic therapy. The molecule is created by combining a miRNA seed sequence with an siRNA sequence to target multiple cellular functions. The siRNA component provides robust disease-related gene regulation. The miRNA component allows the aiRNA to target multiple cellular pathways, giving it an additional method to target disease-related genes. aiRNAs are simple to modify and provide a promising future for cancer and other RNAi-based therapeutics.
Stage of Research
- In vitro study (figure below) of aiRNA with miR-200a (to suppress cell motility) and AKT1-targeting siRNA (to suppress cell proliferation) functions suppress cancer cell motility (A) and proliferation (B) better than the miRNA or siRNA alone in HeLa cells.
- Proof of concept aiRNA with miR-9 (to promote cell motility) and TP53 siRNA (to prevent cell death) functions resists chemotherapy and promotes cancer cell motility in HeLa cells.
- Cancer and other RNAi-based therapies
- Improved efficacy and specificity – molecule is designed to have less off-target effects than siRNA and more robust effects than miRNA alone
- Simple design and delivery
- Modular miRNA and siRNA components can be customized to target other disease-related genes
- Single aiRNA molecule may be easier to package into therapeutics than separate miRNA/siRNA molecules
- Multi-faceted robust therapy
- miRNA component targets multiple genes in the disease pathway and mitigates off-target effects of siRNAs
- siRNA component complements miRNA component to regulate additional disease-related pathways
Jiang Z, Liu W, Wang Y, Gao Z, Gao G, Wang X. Rational design of microRNA-siRNA chimeras for multifunctional target suppression. RNA. 2013;19(12):1745–1754.
Rational design of microRNA-siRNA chimeras for multi-functional target suppression (U.S. Patent Nos. 9,550,989)