A Framework for Individualized Splice-Switching Oligonucleotide Therapy

Our latest study has now been published online in Nature, addressing an important question:

How many patients with genetic disease might be potentially amenable to therapeutic intervention via an individualized ASO approach?

We tackle this question by focusing on a specific subclass of ASOs – splice-switching oligonucleotides that alter patterns of gene splicing, like nusinersen and milasen – in a cohort of individuals with ataxia telangiectasia (as a representative, recessive genetic disorder). We use whole genome sequencing, computational predictions, and experimental validation to demonstrate that 9-15% of individuals with A-T are potentially amenable to splice-modulating treatment. We also illustrate the development and deployment of an investigational ASO therapeutic targeting an amenable, recurrent ATM mutation.

Read the Article

Here

 We are incredibly grateful to our partners at the A-T Children’s Project who led the initiative to create and fund the Global A-T Family Data Platform which was crucial to the analysis done in this paper.

Additionally, we want to say a big thank you to the families who have given their time, support, and trust as participants.

Congratulations to lead co-authors Jinkuk Kim, Sijae Woo, Claudio de Gusmao and Boxun Zhao, all our invaluable collaborators, and our whole team who worked so hard to see this study through!

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