About the Article
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[This article belongs to Volume - 69, Issue - 12]
Published on : 2024-12-11 13:38:22
Article Code: AMJ-11-12-2024-12307
Title : DNA Origami Nanostructures as Precision Delivery Vehicles for CRISPR Ribonucleoproteins in Duchenne Muscular Dystrophy
Author(s) : Dr. Kevin Park
Abstract :
In vivo delivery of CRISPR-Cas9 for Duchenne muscular dystrophy (DMD) requires muscle-specific targeting and
reduced immunogenicity. We designed tubular DNA origami nanostructures (DONs) functionalized with myostatin
derived peptides for sarcolemmal targeting. These DONs encapsulated Cas9-guide RNA ribonucleoproteins (RNPs)
targeting the DMD exon 51 splice site. Intramuscular injection in mdx mice achieved 35% exon skipping in myofibers,
restored dystrophin expression, and improved grip strength by 45%. Unlike viral vectors, DONs elicited minimal
innate immune responses and were cleared within 72 hours. This programmable, non-viral delivery system advances
gene editing therapies for monogenic muscle diseases.