Poster abstracts
Poster number 2 submitted by Daniel Binzel
Thermodynamics and Kinetics of the Three-component Collision of Phi29 pRNA-3WJ Assembly for Nanoparticles Targeting and Therapeutic Delivery to Prostate Cancer
Daniel Binzel (Center for RNA Nanobiotechnology and Nanomedicine; College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry; College of Medicine, Dorothy M. Davis Heart and Lung Research Institute ), Bin Guo (Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX 77030, USA), Peixuan Guo (Center for RNA Nanobiotechnology and Nanomedicine; College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry; College of Medicine, Dorothy M. Davis Heart and Lung Research Institute )
Abstract:
The emerging field of RNA nanotechnology necessitates creation of functional RNA nanoparticles, but has been limited by particle instability. Previously, it was found the three-way junction (3WJ) of the Phi29 DNA packaging motor pRNA was found to be ultra-stable and assemble with ease. The three-way junction is composed of three short oligo RNA strands and proven to be thermodynamically stable. Thermodynamic and kinetics studies found that the pRNA 3WJ formed at a rapid rate creating a single-step three component collision with a lack of dimer intermediate formation while being governed by entropy, instead of enthalpy as commonly seen in RNA duplexes. The 3WJ proved to be stable at high temperatures, ultra-low concentrations, and produced a Gibbs free energy of formation well below other studied RNA structures and motifs. With the high stability and folding efficiency of the pRNA 3WJ, it serves as an ideal platform for RNA nanoparticles. RNA nanoparticles were constructed for the targeting of prostate cancer cells expressing Prostate Specific Membrane Antigen (PSMA) through the addition of an RNA apatmer; and the delivery of anti-miRNA sequences. The resulting nanoparticles remained stable while showing specific entry in PSMA positive cells through cell surface receptor endocytosis. The entry of the nanoparticles allowed for specific delivery against onco-miRNAs. Delivery of anti-miRNAs led to the upregulation of pro-apoptotic genes, and down regulation of anti-apoptotic genes in vitro and in vivo. These findings display RNA nanotechnology can result in stable nanoparticles and result in the specific treatment of cancers, specifically prostate cancer.
References:
1. Binzel DW, Khisamutdinov EF, Guo P. Entropy-driven one-step formation of Phi29 pRNA 3WJ from three RNA fragments. Biochemistry. 2014. 53(14):2221-31.
2. Binzel DW, Khisamutdinov E, Vieweger M, Ortega J, Li J, Guo P. Mechanism of three-component collision to produce ultrastable pRNA three-way junction of Phi29 DNA-packaging motor by kinetic assessment. RNA. 2016 22(11):1710-1718.
3. Binzel DW, Shu Y, Li H, Sun M, Zhang Q, Shu D, Guo B, Guo P. Specific delivery of miRNA for high efficient inhibition of prostate cancer by RNA nanotechnology. Molecular Therapy. 2016. 24(7):1267-77.
Keywords: RNA Nanotechnology, Kinetics, Prostate Cancer