"Nucleic acid drugs" based on oligonucleotides have attracted much attention as a new drug modality for treatment of genetic diseases that have been difficult to modulate with conventional approaches. Conventional nucleic acid drug development has problems with in vivo stability and delivery to target tissues, but with the advancement of modified nucleic acid technology and drug delivery system (DDS), the advanced oligonucleotides with much higher efficacy, safety and excellent pharmacokinetic properties are being achieved. Oligonucleotides are generally synthesized by repeating extension reactions on a solid-phase carrier, then cut out from the carrier, purified by column chromatography and ultrafiltration. For producing oligonucleotides with high-quality, it is very important and challenging work to remove the impurities generated in each reaction steps, which usually having similar molecular size and properties as target product. Therefore, I am engaged in study of protocol optimization for oligonucleotide production.