Spherical nucleic acids as a divergent platform for synthesizing RNA-nanoparticle conjugates through enzymatic ligation

Herein, we describe a rapid, divergent method for using spherical nucleic acids (SNAs) as a universal platform for attaching RNA to DNA-modified nanoparticles using enzyme-mediated techniques. This approach provides a sequence-specific method for the covalent attachment of one or more in vitro transcribed RNAs to a universal SNA scaffold, regardless of RNA sequence. The RNA–nanoparticle constructs are shown to effectively knock down two different gene targets using a single, dual-ligated nanoparticle construct.