Antisense oligonucleotide therapeutics (AOT) are short synthetic DNA or RNA sequences that upon specific hybridization with target RNA induce gene knockdown or gene restoration. For successful implementation AOTs need to fulfil specific requirements such as precise target binding, enzymatic stability and targeted intracellular delivery. We are developing advanced oligonucleotide sequences which have high potential for improved intracellular delivery and to induce gene knockdown effect. Cutting edge technology and methods are used to evaluate the performance of the new probes.