EP 240: Hijacking DNA repair machinery to treat Huntington’s disease with Vincent Dion of the UKDRI

This week on The Genetics Podcast, Patrick is joined by Dr. Vincent Dion, Group Leader at the UK Dementia Research Institute at Cardiff University. They discuss how repeat expansions drive Huntington’s disease and other neurological disorders, why DNA repair can sometimes worsen these mutations over time, and how CRISPR nickase editing could offer a new way to shrink disease-causing repeats rather than simply silence them.Show Notes0:00 Intro to The Genetics Podcast01:00 Welcome to Paul01:40 Long-read sequencing and ancestry-specific APOE4 risk in Alzheimer’s disease04:20 Key findings from Paul’s study on a protective APOE4-linked variant in Alzheimer’s disease10:58 What rare PSEN1 and PSEN2 variants reveal about Alzheimer’s disease biology14:38 Disease-specific genetic mechanisms in ALS versus Alzheimer’s17:14 Precision therapies for neurodegenerative disease18:35 Choosing therapeutic targets in the neurodegenerative disease cascade20:21 Landscape of ALS and Alzheimer’s therapies 23:48 Lessons from liver-directed gene therapy on microRNA toxicity, cancer risk, and brain delivery challenges29:12 Using long-read sequencing to uncover tandem repeat expansions missed by conventional genomics33:26 Findings from a study of long-read sequencing on ancient genomes38:06 Closing remarksPlease consider rating and reviewing us on your chosen podcast listening platform!