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Comment
. 2023 Jun 26;8(1):254.
doi: 10.1038/s41392-023-01526-0.

CRISPRing the hypertrophic cardiomyopathy: correcting one pathogenic variant at a time

Junaid Afzal  1 , Kshitiz  2
Affiliations
Comment

CRISPRing the hypertrophic cardiomyopathy: correcting one pathogenic variant at a time

Junaid Afzal et al. Signal Transduct Target Ther. .
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
a The heterozygous Myh7 gene mutation causes open myosin conformation which results in increased myosin partnership with actin (Na) with accompanying hypercontractility and higher energetic cost. This results in the progressive worsening of the disease phenotype. b Both studies employed the dual AAV9 to deliver ABE-Cas9. c Chai et al. (left-blue arrow) screened the ABE variants with a human sgRNA to choose the variant with minimal bystander/off-target effect. They generated a humanized mice model with the incorporation of the human Myh7 region in the orthologous Myh6 mice gene. Mice pups at PO were injected with AAV9. Cyclosporine A was used to precipitate the disease phenotype. Reichert et al. (right-brown arrow) used ABE8e with sgRNA complementary to the mouse R403Q region in two different R403Q mice models. They injected the mice at d 10–13 (single) or with a second dose of AAV9 at week 2–3. Both studies showed improvement in disease phenotype with correction of pathogenic variants (blue: Chai et al, brown: Reichert et al.), enhanced contractility on echocardiography, and reduced fibrosis on histology. Modest improvement was observed on molecular signature. Created with BioRender.com
See this image and copyright information in PMC

Comment on

References

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