Considerations for Cardiac CRISPR
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- clustered regularly interspaced short palindromic repeats
- CRISPR-Cas systems
- gene editing
- myocytes, cardiac
The recently identified 2-component clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has revolutionized the ease with which genome editing can be performed, greatly simplifying the process of generating knockout animal models.1,2 However, in spite of the great advances made, fewer studies have focused on the efficacy of the system for editing postnatal or adult tissues as a means to model adult onset diseases or to provide potential therapeutic intervention. In particular, the use of the system to perform genome editing in a tissue-specific manner remains to be thoroughly evaluated, especially for tissues that are less amenable to viral delivery of the CRISPR/Cas9 components, a common strategy for delivery in adult tissues.3 Because the heart is responsible for a large disease burden, it represents a particularly attractive tissue to target for therapeutic purposes.4 Although several studies have shown that cardiomyocytes can be edited in the postnatal murine heart using viral delivery of CRISPR/Cas9 system components,5–7 the efficiency of this phenomenon has been less well characterized.
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A study in this issue by Johansen et al8 from Eva van Rooij’s group performed an in-depth analysis of CRISPR/Cas9-mediated gene editing in postnatal mouse myocytes. Cardiac-restricted expression of Cas9 was inducing using mice containing a floxed Cas9 cassette with a GFP (green fluorescent protein) reporter knocked into the Rosa26 locus together with an αMHC-Cre (alpha-myosin heavy chain-Cre) transgene. Consistent with other models that have expressed Cas9 in either a broad or tissue restricted manner,5,6,9 no changes in baseline cardiac function were observed after Cas9 overexpression, suggesting that Cas9 …