Direct CNS Delivery Of Oligonucleotides: Beware Of The Unexpected

The interest in using oligonucleotides to target various diseases has grown exponentially over the past five-to-ten years.

Oligonucleotides – short sequences of synthetic DNA or RNA that rely on the natural structure of DNA or RNA – serve as a starting point for various therapeutic modalities such as Antisense Oligonucleotides (ASO), short interfering RNA (siRNA), and microRNA. The use of Oligos allows for precision in personalized medicine approaches, and they have been thought of to have minimal or at least predictable off-target effects.

However, as we gain more experience in the CNS ASO administration field, we are beginning to see unexpected scenarios arising despite using “well-understood” oligonucleotide backbones.