title: A case study: oligonucleotide purification from gram to hundred gram scale.
abstract: This article describes the purification and scale-up of ISIS 2302, a 20-mer phosphorothioate oligonucleotide by anion-exchange (AX) chromatography. The key operating parameters were optimized at gram scale and further scaled up to hundred gram. SOURCE 30Q, a high efficiency polymeric chromatographic media was used for both the small and large-scale work. High length-based purity and yield were maintained at scale-up. This purification is one of the largest demonstrations of AX purification of phosphorothioate oligonucleotide.
authors.affiliation: Isis Pharmaceuticals, Inc., 2292 Faraday Ave., Carlsbad, California 92008, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Deshmukh
authors.forename: K O
authors.initials: KO
authors.lastname: Eriksson
authors.forename: P
authors.initials: P
authors.lastname: Moore
authors.forename: D L
authors.initials: DL
authors.lastname: Cole
authors.forename: Y S
authors.initials: YS
authors.lastname: Sanghvi
mesh_terms: D002852:Chromatography, Ion Exchange / Q000379:methods; D005765:Gastrointestinal Agents / Q000302:isolation & purification; D006358:Hot Temperature; D007166:Immunosuppressive Agents / Q000302:isolation & purification; D020319:Oligodeoxyribonucleotides, Antisense / Q000302:isolation & purification*; D054735:Phosphorothioate Oligonucleotides; D010865:Pilot Projects; D012997:Solvents; D013678:Technology, Pharmaceutical / Q000379:methods*; D013873:Thionucleotides / Q000302:isolation & purification*
chemical_list: D005765:Gastrointestinal Agents; D007166:Immunosuppressive Agents; D020319:Oligodeoxyribonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; D012997:Solvents; D013873:Thionucleotides; C089753:alicaforsen