MicroRNA Pools Synthesized Using Tandem Solid-Phase Oligonucleotide Synthesis

Herein, we describe a new approach to make pools of microRNAtargetingbreast cancer cells. The microRNA pools were synthesized at once onthe same solid support using the "Tandem Oligonucleotide Synthesis"strategy. We make up to four consecutive microRNAs (miR129-1-5p, miR31,miR206, and miR27b-3p) using 2 & PRIME;/3 & PRIME;OAc nucleotide phosphoramidites,with the total length of the pool reaching 88 nucleotides. The developedphosphoramidites, when combined, give a cleavable moiety that separatesthe microRNAs and is cleaved using standard post-RNA synthesis cleavageconditions. Furthermore, we investigate making branched pools (microRNAdendrimers) versus linear pools as a strategy to further improve theproduct yields. Our approach provides with microRNA pools in highyields, which is of relevance to the growing demand on synthetic RNAoligomers for nucleic acid research and technology.