For many applications it is desirable to increase the nuclease stability of the RNA. The most common approach is to substitute canonical bases with 2’-fluoro modified NTPs. Bacteriophage polymerases do not efficiently incorporate 2’ modified NTPs. However, selection strategies have been utilized to evolve polymerases that can incorporate 2’ modified NTPs. Researchers commonly substitute pyrimidine bases with 2’ fluoro modified bases when making RNAs for biological applications, such as aptamers.