Timothy A. Vickers

TL;DR: In this paper, a comparative study of optimized antisense oligonucleotides designed to work by an RNA interference mechanism to oligon nucleotide-dependent mechanisms in human cells was performed and the potency, maximal effectiveness, duration of action, and sequence specificity of optimized RNase H-dependent oligonuclotide and small interfering RNA (siRNA) oligoneucleotide duplexes were evaluated and found to be comparable.

TL;DR: The results show that the high-resolution ASO-tiling approach can identify cis-elements that modulate splicing positively or negatively and highlight the therapeutic potential of some of these ASOs in the context of SMA.

TL;DR: Although PS-ASOs function in both the cytoplasm and nucleus, localization to different subcellular regions can affect their therapeutic potency and the main proteins involved in these processes have been identified and intracellular sites in which PS ASOs are active, or inactive, cataloged.

TL;DR: A large number of ASOs with a 2′-O-methoxy-ethyl ribose (MOE) backbone that hybridize to different positions of SMN2 exon 7 increase full-length SMN protein levels, demonstrating that they do not interfere with mRNA export or translation, despite hybridizing to an exon.

TL;DR: The study of the antisense strand of siRNAs demonstrated that activity depends on the position of the modifications in the sequence, and guidelines to design effective and stable si RNAs for RNA interference mediated therapeutic applications are provided.