spacer
home > ebr > autumn 2018 > produce potential
PUBLICATIONS
European Biopharmaceutical Review

Produce Potential

Custom-made oligonucleotides are commonly produced by solid phase synthesis, where the sequence is grown chemically on a resin in a 3’-5’ direction (1). Each amidite/nucleotide monomer has a 5’ trityl-blocking group to prevent addition of more than one nucleotide in each synthesis step that is cleaved off prior to the start of next coupling reaction (2). The completed oligonucleotide is released from the solid support by ammonolysis. Although the solid-phase technology gives a very low synthesis error rate, a small percentage of sequences where the oligonucleotide has deletions are always present, such as N-1 sequences and depurinations (where the nucleic base has been cleaved off), or extra insertions of elements (eg, N+1) (3). The frequency of failures increases with length of the synthesised oligonucleotide.

Antisense oligonucleotides (ASOs) are DNA sequences designed to bind complementary RNA targets (mainly mRNAs) to affect gene expression. Antisense gene therapy is emerging as one of the most promising therapeutics for various diseases, such as cancer (4-5). As of 2017, six FDAapproved ASO-based therapies are on the market, and many are in clinical trials (6). Most of the ASO molecules currently in clinical trials are phosphorothioates: modified nucleic acids in which one of the non-bridging oxygens on the phosphate backbone is replaced by a sulphur (7). This modification increases the half-life of the oligonucleotide. In addition to the mentioned synthesis errors, the phosphorothioate linkage of phophorotioates might be oxidised to a phosphodiester linkage, (P=O)x.

Due to the stringent requirements in therapeutic applications, efficient purification schemes to produce oligonucleotides with a minimum of erroneous sequences are a necessity.

Read full article from PDF >>

Rate this article You must be a member of the site to make a vote.  
Average rating:
0
     

There are no comments in regards to this article.

spacer
Dr Cecilia Unoson is a Senior Application Scientist at Bio-Works Technologies and has a PhD from the Department of Cellular and Molecular Biology at Uppsala University, Sweden. Cecilia has 15 years’ experience working with oligonucleotides, especially within the RNA field, where she has focussed on regulatory RNAs and the CRISPR-Cas9 system. She also has a strong background in proteomics and has worked in both small and large biotech companies. Today, Cecilia is responsible for the oligonucleotide applications at Bio-Works Technologies.

Dr Lars Haneskog is the R&D director at Bio-Works Technologies, with a PhD in bioseparation and membrane proteins from Uppsala University, Sweden. The research focus was bioseparation and membrane proteins. He has more than 20 years of experience in chromatographic purification of biomolecules, and development of chromatography products.
spacer
Dr Cecilia Unoson
spacer
spacer
spacer
Dr Lars Haneskog
spacer
spacer
Print this page
Send to a friend
Privacy statement
News and Press Releases

Haselmeier Relies on DQIQOQ Qualified Testing Machines and Zwicks Materials Testing Laboratory

Haselmeier is a leader in the development and manufacture of innovative self injection devices. Numerous international pharmaceutical manufacturers are customers of this Swiss company. In addition to testing production batches of pen injectors, Zwick's Materials Testing Laboratory offers DQ/IQ/OQ qualification and measurement system analysis of the testing system used for the tests.
More info >>

White Papers

Interface: Drug Delivery Devices

Phillips-Medisize

A family is packing for its annual summer trek to the cottage by the lake. Along with fishing gear, sunscreen, and life vests, the checklist also includes another kind of life saver – an autoinjector that delivers two doses of epinephrine to treat anaphylaxis, a severe and potentially lifethreatening allergic reaction.
More info >>

 
Industry Events

Partnerships in Clinical Trials Europe 2018

27-29 November 2018, CCIB, Barcelona

Partnerships in Clinical Trials Europe is back – and bigger than ever. Europe’s most complete clinical meeting is bringing together 1000+ of the industry’s leading experts this November for it’s 17th annual gathering, and you’re invited!
More info >>

 

 

©2000-2011 Samedan Ltd.
Add to favourites

Print this page

Send to a friend
Privacy statement