Poster abstracts

Poster number 50 submitted by Xijun Piao

Fundamental Study on Nucleic Acid Three-way Junction Inspired by phi29 Bacteriophage Packaging RNA

Xijun Piao (College of Pharmacy), Hongran Yin (College of Pharmacy), Zhefeng Li (College of Pharmacy), Congcong Xu (College of Pharmacy), Hongzhi Wang, Daniel Binzel, Daniel Jasinski, (College of Pharmacy), Peixuan Guo (Center for RNA Nanobiotechnology and Nanomedicine; College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry; College of Medicine, Department of Physiology & Cell Biology)

Abstract:
RNA three-way junction is common in nature and the three-way junction in phi29 bacteriophage packaging RNA has recently been used as the core in RNA nanotechnology for treatments of various cancers for the reasons listed below: 1) anionic charge disallows nonspecific passage across negatively charged cell membrane; 2) RNA nanoparticles can be readily functionalized with RNA aptamer to enhance the homing of RNA nanoparticles to cancer cells; 3) nanoscale size and shape avoids rapid renal clearance and engulfment by lung macrophages and liver Kupffer cells; 4) RNA nanoparticles show favorable biodistribution profiles with little accumulation in healthy organs, minimizing nonspecific side effects. DNA, RNA and 2’-F 3WJs have previously been studied in our group. To fully characterize phi29 3WJ and promote RNA nanotechnology, this study incorporates two well-known nuclease-resistant oligonucleotides, phosphorothioate DNA (PS DNA) and locked nucleic acid (LNA). In excellent agreement with duplex system, the thermostability trend of these five oligonucleotides within phi29 3WJ is PS DNA < DNA < RNA < 2’-F < LNA. LNA 3WJ shows significant resistance to heat or 8 M urea denaturation, as well as serum degradation. LNA 3WJ inspired by phi29 bacteriophage pRNA shows potential as a novel drug delivery platform.

References:
1) Shu, D.; Shu, Y.; Haque, F.; Abdelmawla, S.; and Guo, P. (2011)
Thermodynamically stable RNA three-way junctions for constructing
multifuntional nanoparticles for delivery of therapeutics. Nat. Nanotechnol.
6, 658−667.
2)Binzel, D. W.; Khisamutdinov, E.F.; Guo, P. (2014) Entropy-driven one-step
formation of Phi29 pRNA 3WJ from three RNA fragments.
Biochemistry 53, 2221–2231.

Keywords: phi29 three-way junction, RNA nanotechnology, thermodynamic stability