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. 2023 Jul;3(3):28.
doi: 10.20517/jca.2023.19. Epub 2023 Jun 16.

Editing the trajectory of hypertrophic cardiomyopathy

Mason E Sweat  1 , William T Pu  1   2
Affiliations

Editing the trajectory of hypertrophic cardiomyopathy

Mason E Sweat et al. J Cardiovasc Aging. 2023 Jul.
No abstract available

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Conflict of interest statement

Conflicts of interests Both authors declared that there are no conflicts of interest.

Figures

Figure 1.
Figure 1.
Base editing for HCM caused by the MYH7R403Q pathogenic variant. The sequences of wild-type and R403Q MYH7 near the pathogenic variant are shown, along with a schematic of the adenine base editing system. The base editor is targeted to the R403Q allele by a specific guide RNA (green line). Three types of edits are possible: 1. on-target reversion of the pathogenic “A” (red) to “G” (green), converting the HCM allele into a normal allele; 2. Bystander editing, where another adenine near the targeted residue, most often within an “editing window” (light blue) is converted to G (purple), introducing additional missense changes into the encoded protein; and 3. Off-target editing. This occurs when the guide RNA targets the base editor to other regions in the genome. The relative frequency of on-target vs bystander and off-target editing is a major determinant of benefit vs. risk of base editing. Successful editing ameliorated pathological HCM phenotypes in human iPSC-CM and mouse models of HCM caused by MYH7R403Q.
See this image and copyright information in PMC

References

    1. Marian AJ, Braunwald E. Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ Res 2017;121:749–70. - PMC - PubMed
    1. Olivotto I, Oreziak A, Barriales-Villa R, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2020;396:759–69. - PubMed
    1. Chai AC, Cui M, Chemello F, et al. Base editing correction of hypertrophic cardiomyopathy in human cardiomyocytes and humanized mice. Nat Med 2023;29:401–11. - PMC - PubMed
    1. Reichart D, Newby GA, Wakimoto H, et al. Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice. Nat Med 2023;29:412–21. - PMC - PubMed
    1. Geisterfer-Lowrance AA, Christe M, Conner DA, et al. A mouse model of familial hypertrophic cardiomyopathy. Science 1996;272:731–4. - PubMed

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