The University of Cincinnati (UC) researchers have discovered a RNA nano-scaffold that is thermodynamically stable in the body. This discovery further leads to the advancement of therapeutic RNA nanotechnology.
The researchers have reported the creation of a RNA nanoparticle in the Nature Nanotechnology journal. Peixuan Guo, one of the researchers, stated that the nanoparticle developed from packaging RNA (pRNA) molecules’ three-way junction (3WJ) motif, can function as a base for constructing huge, multifunctional nanoparticles, which can be used a carrier to supply therapeutics to targeted cells.
During the research, the researchers studied the novel structure of bacteriophage phi29’s DNA packaging motor. The motor is accelerated by a ring of pRNA molecules having helical domains and interlocking loops that are connected firmly by a robust 3WJ motif.
The researchers reproduced the 3WJ core utilizing three tiny RNA fragments that have a high tendency for assembling into huge structures. Moreover, the 3WJ core’s each arm can be attached to receptor-binding ligands, siRNA molecules and RNA aptamers, which are molecular tools needed for the nanoparticles to detect the targeted cell and silence its genes. The developed nanoparticle sustained its stability and operational in vitro and while brought in vivo, it exclusively targets tumor cells without affecting other normal tissues and critical organs.
Guo commented that developing RNA or DNA fusion complexes is not difficult but making sure that proper folding of individual molecules is done inside the complex to ensure their function is maintained subsequent to fusion is a complicated task. The pRNA 3WJ core guides individual functional modules’ folding and the 3WJ core’s stability ensures that every fusion module stays folded for appropriate functionality, he added.