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Don Cleveland, PHD

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Don Cleveland, PhD

Ludwig Institute of Cancer Research/ University of California, San Diego

Identifying the molecular mechanism of therapeutic uptake of antisense oligonucleotides, using a genome-scale CRISPR-Cas9 mediated gene activation strategy
Co-funded with Ionis Pharmaceuticals

Work initiated by us, in conjunction with Ionis Pharmaceuticals, to apply antisense oligonucleotide therapeutic strategies to ALS-causing genes (and other diseases of the central nervous system) represents an attractive, feasible approach to therapy, with a pipeline of designer DNA based drugs that are either currently in clinical trial or imminently scheduled, and are among the best current hopes for treatment of ALS. The clinical success of ASOs in spinal muscular atrophy is very encouraging, but the mechanism for effective uptake by cells into the brain parenchyma and spinal cord remains entirely unknown. Herein we propose to apply CRISPR based genome-scale activation screening to identify the genes and pathways responsible for ASO uptake as the crucial next step to improve delivery and efficacy of ASO therapies within the central nervous system.


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Steven Finkbeiner

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Gladstone Institutes, UCSF
Two recently discovered genes that have been associated with both familial and sporadic forms of ALS encode the related proteins TDP43 and FUS cause neuron death in ALS.
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