Although aptamers are a new entry, the broader field of therapeutic oligonucleotides has been around for about 20 years, beginning with antisense oligonucleotides in the 1980s. As a result, a great deal of technology investment has been made in medicinal chemistry, chemical process development, and analytical chemistry that has enabled the efficient manufacture of therapeutic oligonucleotides of high quality. Oligonucleotides are made by solid-phase chemical synthesis that involves the progressive addition of the appropriate nucleotide to the growing chain. This process is well defined using commercially available instrumentation and raw materials. A great strength of aptamer technology is the ability to rapidly scale the synthesis process and move from milligram to gram to kilogram scale very quickly. The discovery and development teams do not have significant delays waiting for drug. This is in contrast to biotherapeutics (such as monoclonal antibodies) where large timeline delays are incurred during cell line development and material scale-up. Recent advances in analytical chemistry tools and techniques have enabled an improved ability to characterize both the raw materials and the end product of therapeutic oligonucleotides. As our ability to resolve impurities in our raw materials and drugs improves, we introduce process improvements that allow us to continuously improve the quality of our products. The same analytical tools enable us to build a detailed understanding of stability and thereby ensure a quality product throughout the stated shelf life. Even though oligonucleotide manufacture and characterization is relatively well understood and utilizes established technologies, the know-how is consolidated into the few companies that have specialized in this field. Archemix has assembled a team of highly specialized scientists in this area and brings this know-how to support our internal programs and our partnerships. |
Click image to view an animation of solid phase synthesis, cleavage, and deprotection of an aptamer. |
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Aptamer Discovery