My objective is to design control experiments to antisense oligonucleotides action.
As part of control assays, I intend to use oligonucleotides differing from
the original antisense moiety by a limited number of mismatches. These mutations
are introduced to destabilize duplex formation between the target RNA and the
oligonucleotide, and avoid specific antisense effects.
Problems arise when considering how to choose mismatch positions and number,
being clear that the closer to the original the better. A calculation of duplex stability
seem necessary for each one of the possible alterations to the original sequence.
The problem is comparable with the search for the "worst" hybridization probe.
I tried using OLIGO 4.0, but the program is unable to accept mismatched probes.
So, if you have or heard about software able to solve the problem, please contact.
Thank you in advance.
