Toward CRISPR Therapies for Cardiomyopathies

Article Multidisciplinary Sciences

In vivo base editing rescues Hutchinson-Gilford progeria syndrome in mice

Luke W. Koblan et al.

Summary: Using adenine base editor (ABE), researchers successfully corrected the pathogenic mutation in fibroblasts from children with Hutchinson-Gilford progeria syndrome, mitigating RNA mis-splicing, reducing progerin levels, and correcting nuclear abnormalities. In vivo base editing with AAV9 encoding ABE in transgenic mice resulted in substantial, durable correction of the mutation, restoration of normal RNA splicing, and improvement of vascular pathology, ultimately extending the lifespan of the mice. These findings demonstrate the potential of in vivo base editing as a treatment for genetic diseases.

NATURE (2021)

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Article Multidisciplinary Sciences

In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates

Kiran Musunuru et al.

Summary: This study demonstrates the efficient and precise modification of disease-related genes in living cynomolgus monkeys using CRISPR base editors delivered in vivo via lipid nanoparticles. The results provide proof-of-concept for the potential therapeutic application of CRISPR base editors in making precise single-nucleotide changes in target genes, supporting a 'once-and-done' approach for the treatment of diseases.

NATURE (2021)

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Article Multidisciplinary Sciences

Precise correction of Duchenne muscular dystrophy exon deletion mutations by base and prime editing

F. Chemello et al.

Summary: This study demonstrated the use of adenine base editor to restore dystrophin expression in cardiomyocytes affected by Duchenne muscular dystrophy mutation, as well as reframing the dystrophin open reading frame. In vivo experiments with mice showed successful gene editing and disease correction, indicating the potential of nucleotide editing for diverse DMD mutations with minimal genome modification.

SCIENCE ADVANCES (2021)

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Review Cell Biology