Webinars
Date: February 26, 2026
Time: 11am-12pm EST / 5-6pm CET
Title: Combinational modulation of DNA Mismatch Repair protein ratios alter CAG repeat instability in hTERT-RPE1 cellular model
Description:
The somatic expansion of an unstable CAG trinucleotide repeat tract located within the first exon of the Huntingtin gene is the primary cause of Huntington’s disease. This somatic instability is driven by elements of the DNA mismatch repair (MMR) pathway which serve to expand the number of CAG trinucleotides accumulated over time. The MMR pathway comprises multiple characteristically different protein complexes that interact with unstable CAG repeat structures in distinct ways. Modulating MMR protein expression with short interfering RNA (siRNA) significantly alters CAG repeat instability in both Huntington’s disease mouse models and artificial cellular CAG repeat models like hTERT-RPE1-CAG. The emerging therapeutic use of siRNA to influence the activity of specific MMR elements offers a promising path toward disease-modifying treatments for Huntington’s disease.
Speaker:
Title: Tailoring Antisense Oligonucleotide Manufacturing to N-of-1 Needs
Description:
Following the landmark development of Milasen in 2018—the first N-of-1 antisense oligonucleotide (ASO) created specifically for a single patient—more than 20 individualized ASOs have since been developed to treat over 30 rare-disease patients worldwide.
This rapid growth has introduced a new challenge: how to manufacture oligonucleotides tailored uniquely to each patient.
To meet this need, an example standardized approach is developed for manufacturing splice-switching ASOs for neurological disorders, typically 18–22 nucleotides long and built with a consistent set of chemical modifications.
This emerging framework represents a true platform technology, raising a central scientific question: can diverse ASO sequences be reliably manufactured using the same set of unit operations and controlled conditions?
