Antisense oligonucleotides—or ASOs—are short, synthetic, single-stranded oligonucleotides extensively used for altering RNA expression to reduce, restore, or modify protein expression via several distinct mechanisms. With possible applications extending to both neurological and non-neurological conditions, there is great potential for valuable new therapeutics.

Developing robust bioanalytical assays is essential for accurately quantifying ASOs within intricate biological matrices, including eye, liver, or brain tissues, and these assays must exhibit high sensitivity to detect ASOs at low concentrations while simultaneously being immune to interference from other components in the sample. Hybridization-based assays have emerged as reliable and effective methods for precisely quantifying ASOs both in circulation and within targeted tissues.

In Issue 12 of The Altascientist, we explore advances in hybridization-based assays more deeply, in addition to:

• regulatory considerations
• case studies
• bioanalytical considerations, including:
  • ADAs and metabolite interference
  • ASO quantitation in tissues
  • method sensitivity

This issue also features two case studies about resolving challenges with matrix effect and about stability of ASOs in tissue matrix.