A case study: oligonucleotide purification from gram to hundred gram scale.
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.
Deshmukh
R R
RR
Isis Pharmaceuticals, Inc., 2292 Faraday Ave., Carlsbad, California 92008, USA.
Eriksson
K O
KO
Moore
P
P
Cole
D L
DL
Sanghvi
Y S
YS
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*
D005765:Gastrointestinal Agents; D007166:Immunosuppressive Agents; D020319:Oligodeoxyribonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; D012997:Solvents; D013873:Thionucleotides; C089753:alicaforsen