Compared to other biomolecules, RNA molecules are unstable and transient. Foreign RNA molecules, when introduced to human body, have limited protein expression level in cell and often trigger immunogenicity in the body. However, these practical problems can often be mitigated by various optimizations on RNA molecules, including chemical modifications, mRNA Cap/codon/tail optimization, etc. Leveraging the unique aspect with both chemical and biological information of the CAS Content Collection, this paper focuses on chemical modifications to the base, backbone, sugar, and 5' or 3' ligations to other molecules. While chemical modifications increase RNA stability, complexes of RNA within nanoparticles provide further protection. Except for aptamers that bind to a cell surface target, RNA must be delivered into the cell by a carrier. After the RNA is internalized, it must be released from the membrane-bound vesicle or endosome to the cytosol. Without a doubt, the delivery system has been an important research topic for RNA medicine.