The chemical modifications that AM Biotech uses improve existing aptamer and siRNA performance. DNA or RNA aptamer binding affinity can improve by orders of magnitude by using just one or two modified nucleotides in just one or two sequence locations – without adversely affecting specificity.
AM Biotech uses a high throughput synthesizer to systematically walk modified nucleotides through an existing aptamer or siRNA sequence. Each sequence variant is screened by either the customer or AM Biotech to determine if it improves performance. The modification locations that improve performance can be combined in a more focused second synthesis to test for additional improvement.
Do you have an aptamer or siRNA sequence that you want to improve?
Please contact AM Biotech for more information or for a quote for improving your existing aptamer or siRNA sequence.
Chemical Diversity = Better Aptamer Performance
FAQ: Aptamer Improvement
An aptamer made from standard DNA or RNA (inclusive of modifications to enhance stability against nucleases) can benefit from more functional groups that enhance interaction with the target. Inserting the right functional groups in the right locations can improve binding affinity by 1000X. Typically, this improvement in binding affinity does not negatively affect specificity; in fact, it may improve specificity in some cases.
AM Biotech has found that amino acid functional groups play an important role in target interaction. Additionally, the phosphorodithioate (PS2) modification has demonstrated extraordinary improvement in target interaction when used strategically. The replacement of just a single PS2 modification for the normal phosphate ester into an existing RNA aptamer may enhance its binding affinity by 1000-fold.
First, we find the minimum portion of the sequence required for binding to the target. Then we synthesize numerous variants that ‘walk’ a modification through the shortened sequence and test each variant for performance. This is rather cumbersome process, but is currently the most effective way to identify the sequence locations where modifications can make a major difference. The shortened sequence can also reduce synthesis cost and improve yield.
FAQ: Improving siRNA
AM Biotech has demonstrated that certain 2’-OMe-PS2 modifications to siRNA can significantly improve gene silencing. The chemistry also improves the half-life of the siRNA in vivo by making the oligo more resistant to nuclease degradation.
The 2’-OMe-PS2 modification appears to significantly enhance silencing in a particular sequence ‘motif’. However, only a few motifs have been tested to date. Contact AM Biotech to find out if your siRNA matches the motif that we have found to be the most receptive to 2’-OMe-PS2 modification enhancement.
We synthesize numerous variants that ‘walk’ the PS2 modification through the sequence. We then send you the variants to test. If the modification if found to enhance efficacy in more than one sequence location, the additional variants are synthesized and sent to you for testing that include combinations of the modified sequence locations.