Our approach is simple, versatile, and broadly applicable, as evidenced by the successful enhancement of ASO activity across different backbone chemistries, different targets, and different mechanisms of action. Thus, our technology is robust and potentially applicable to a wide range of therapeutic scenarios. Notably, we have taken Oblimersen, an 'almost-therapeutic' ASO, and used our approach to dramatically improve its therapeutic efficacy. This improvement suggests that our work has the potential to transform other suboptimal ASO drugs into more effective therapeutics.